Title of Invention

A DOSAGE FORM

Abstract A dosage form containing at least one active ingredient, which comprises a core and a shell surrounding at least a portion of the core, wherein the core has a density of at least 0.9 g/cc, the shell comprises one or more openings, the shell is readily soluble in gastrointestinal fluids, and the dosage form provides for immediate release of at least one active ingredient upon contact of the dosage form with a liquid medium wherein the dosage form provides for immediate release of at least one active ingredient contained in the core which comprises a compressed tablet.
Full Text CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part of PCT Application Nos. PCT/US02/31129,
filed September 28,2002; PCT/US02/31117, filed September 28,2002;
PCT/US02/31062, filed September 28,2002; PCT/US02/31024, filed September 28,
2002; and PCT/US02/31163, filed September 28,2002, which are each continuations-
in-part of USSN 09/966,939, fifed September 28,2001; USSN 09/966,509, filed
September 28,2001; USSN 09/966,497, filed September 28,2001; USSN 09/967,414,
filed September 28,2001; and USSN 09/966,450, filed September 28, the disclosures
of all of the above which is incorporated herein by reference in its entirety.
Field of the Invention
This invention relates to a dosage form providing immediate release of an
active ingredient. The dosage form comprises a solid core and a shell surrounding the
core. The shell has one or more openings therein.
Background of the Invention
Certain dosage forms containing apertures or embossments are known. For
instance, "osmotic pump" dosage forms for the administration of pharmaceutically
active ingredients are known in the art. They typically comprise a semipermeable
wall that surrounds a reservoir containing drug. The wall is permeable to the passage
of an external fluid, impermeable to the passage of drug, and has a passageway
through the semipermeable wall for delivering drug from the osmotic system. For
example, U.S. Patent No. 4,576,604 discloses an osmotic device comprising a drug
compartment surrounded by a wall (coating) having a passageway therein. The wall
may comprise an immediate release dose of drug, and the inner drug compartment
may comprise a sustained release dose of drug.
U.S. Patent No. 4,449,983 discloses another osmotic device comprising two,
separately housed drugs that are separately dispensed from the device. The device
comprises two compartments, one for each drug, separated by a partition. Each
compartment has an orifice for communicating with the exterior of the device.
U.S. Patent No. 3,823,816 discloses a water-soluble package provided in the
form of a hard shell capsule filled with powder, granules, or the like. The capsule is
apertured, and the apertures are covered by a water-soluble barrier film. The film is
more water soluble than the capsule so that when the package contacts water, the film
rather than the capsule dissolves first, exposing the contents for dissolution and/or
release by way of the apertures while the capsule is intact.
U.S. Patent No. 5,256,440 relates to an intagliated dosage form comprising
one or more circumscribed regions on its surface. The dosage form is spray coated
with a latex polymer. When placed in an environment of use, the latex coating within
the circumscribed region is reproducibly expelled, leaving a coated core tablet with a
predefined aperture, which exposes a discrete portion of the core surface to the
environment of use.
One known method of producing gelatin coated dosage forms is via an
enrobing process wherein two separate films made of gelatinous material are applied
to opposite sides of a tablet by a pair of rotary dies, as disclosed for example, in U.S.
Patent Nos. 5,146,730 and 5,459,983. Film formulations for producing gelcaps and
geltabs prepared via enrobing methods such as those disclosed in U.S. Patent Nos.
5,146,730 and 5,459,983 typically comprises a water-based gelatin preparation having
about 45% gelatin and about 9% plasticizer (glycerin and/or sorbitol) by weight.
Glycerin and sorbitol can be used as single plasticizers or in combination with each
other.. In addition, other sugars and poly-hydroxy compounds can be used as
additives and plasticizers. If a tamper-evident gelatin-coated medicine tablet is the
desired end product, then the ratio of plasticizer to gelatin in the gelatin formulation
should be in the range of about 1:5.
Another conventional method for forming a shell (or coating), on a core (or
substrate), is mat disclosed in WO 01/57144 which utilizes the principles of
electrostatic deposition to form the coating. At least one of the core or the shell
preferably incorporates one or more "charge control agents," such as metal saJicylates,
selected from propionic acid derivative NSAID, e.g. ibuprofen, naproxen,
flurbiprofen, fenbufen, fenoprofen, indoprofen, ketoprofen, fhuprofen, pirprofen,
carprofen, oxaprozin, pranoprofen, suprofen, and phannaceutically acceptable salts,
derivatives, and combinations thereof. In another particular embodiment of the
invention, the active ingredient may be selected from acetaminophen, acetyl salicylic
acid, ibuprofen, naproxen, ketoprofen, flurbiprofen, diclofenac, cyclobenzaprine,
meloxicam, rofecoxib, celecoxib, and pharmaceutically acceptable salts, esters,
isomers, and mixtures thereof.
In another embodiment of the invention, the active ingredient may be selected
from pseudoephedrine, phenylpropanolamine, chlorpheniramme, dextromethorphan,
diphenhydramine, astemizole, terfenadine, fexofenadine, loratadine, desloratadine,
cetirizine, mixtures thereof and pharmaceutically acceptable salts, esters, isomers, and
mixtures thereof.
Examples of suitable polydimethylsiloxanes, which include, but are not
limited to dimethicone and simethicone, are those disclosed in United States Patent
Nos. 4,906,478, 5,275,822, and 6,103,260, the contents of each is expressly
incorporated herein by reference. As used herein, the term "simethicone" refers to the
broader class of polydimethylsiloxanes, including but not limited to simethicone and
dimethicone.
The active ingredient or ingredients are present in the dosage form in a
therapeutically effective amount, which is an amount that produces the desired
therapeutic response upon oral administration and can be readily determined by one
skilled in the art. In determining such amounts, the particular active ingredient being
administered, the bioavailability characteristics of the active ingredient, the dosing
regimen, the age and weight of the patient, and other factors must be considered, as
known in the art. Typically, the dosage form comprises at least about 1 weight
percent, preferably, the dosage form comprises at least about 5 weight percent, e.g. at
least about 25 weight percent of a combination of one or more active ingredients. In
one preferred embodiment, a core comprises a total of at least about 50 weight
for example zinc salicylate, magnesium salicylate and calcium salicylate; quaternary
ammonium salts; benzalkonium chloride; benzethonium chloride; trimethyl tetradecyl
ammonium bromide (cetrimide); and cyclodextrins and their adducts, in an amount
from about 1% to about 10% by weight of the shell.
Applicants have now discovered that an immediate release dosage form may
be made from a solid core and a shell surrounding the core, wherein the core has a
density of at least about 0.9 g/cc. The shell comprises one or more openings therein
and is readily soluble in gastrointestinal fluids. The shell is preferably applied to the
core by enrobing.
Summary of the Invention
The present invention provides a dosage form containing at least one active
ingredient, which comprises a core and a shell surrounding the core, wherein the core
has a density of at least about 0.9 g/cc, the shell comprises one or more openings, the
shell is readily soluble in gastrointestinal fluids, and the dosage form provides for
immediate release of at least one active ingredient upon contact of the dosage form
with a liquid medium.
The invention also provides a dosage form comprising a core having an outer
surface and a shell having outer and inner surfaces, wherein at least a portion of the
shell surrounds the core such that the shell inner surface resides substantially
conformally upon the core outer surface, at least a portion of the shell comprises one
or more openings therein, one or more of the openings are from about 200 to about
2000 microns in diameter or width, at least a portion of the shell is readily soluble in
gastrointestinal fluids, the average shell thickness is in the range from about 100 to
about 400 microns, the shell comprises less than about 50% crystallizable sugar, and
the dosage form is substantially free of charge control agents and the dosage form
Suitable oral care agents include breath fresheners, tooth whiteners,
antimicrobial agents, tooth mineralizers, tooth decay inhibitors, topical anesthetics,
mucoprotectants, and the like.
Suitable flavorants include menthol, peppermint, mint flavors, fruit flavors,
chocolate, vanilla, bubblegum flavors, coffee flavors, liqueur flavors and
combinations and the like.
Examples of suitable gastrointestinal agents include antacids such as calcium
carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate,
aluminum hydroxide, sodium bicarbonate, dihydroxyaluminum sodium carbonate;
stimulant laxatives, such as bisacodyl, cascara sagrada, danthron, senna,
phenolphthalein, aloe, castor oil, ricinoleic acid, and dehydrocholic acid, and mixtures
thereof; H2 receptor antagonists, such as famotadine, ranitidine, cimetadine,
nizatidine; proton pump inhibitors such as omeprazole or lansoprazole;
gastrointestinal cytoprotectives, such as sucraflate and misoprostol; gastrointestinal
prokinetics, such as prucalopride, antibiotics for H. pylori, such as clarithromycin,
amoxicillin, tetracycline, and metronidazole; antidiarrheals, such as diphenoxylate
and loperamide; glycopyrrolate; antiemetics, such as ondansetron, analgesics, such as
mesalamine.
In one embodiment of the invention, the active ingredient may be selected
from bisacodyl, famotadine, ranitidine, cimetidine, prucalopride, diphenoxylate,
loperamide, lactase, mesalamine, bismuth, antacids, and pharmaceutically acceptable
salts, esters, isomers, and mixtures thereof.
In another embodiment, the active ingredient is selected from analgesics, anti-
inflammatories, and antipyretics, e.g. non-steroidal anti-inflammatory drugs
(NSAIDs), including propionic acid derivatives, e.g. ibuprofen, naproxen, ketoprofen
and the like; acetic acid derivatives, e.g. indomethacin, diclofenac, sulindac, tolmetin,
and the like; fenamic acid derivatives, e.g. mefanamic acid, meclofenamic acid,
flufenamic acid, and the Uke; biphenylcarbodylic acid derivatives, e.g. diflunisal,
flufenisal, and the Uke; and oxicams, e.g. piroxicam, sudoxicam, isoxicam,
meloxicam, and the Uke. In one particular embodiment, the active ingredient is
provides for immediate release of at least one active ingredient upon contact of the
dosage form with a liquid medium.
Brief Description of Accompanying Drawings
Figures 1-5 depict dosage forms according to the invention.
Figure 6 depicts various openings according to the invention.
Figure 7 depicts a method of producing a dosage form according to the
invention using an enrobing process.
Figure 8 depicts another method of producing a dosage form according to the
invention using an enrobing process.
Figure 9 depicts a further method of producing a dosage form according to the
invention using an enrobing process.
Figure 10 depicts a method of producing a dosage form according to the
invention using an enrobing process with a capsule comprising openings.
Figure 11 depicts a method of producing a dosage form according to the
invention using a dipping process.
Figure 12 depicts another method of producing a dosage form according to the
invention using a dipping process.
Figure 13 depicts a method of producing a dosage form according to the
invention using a transfer process.
Figure 14 depicts a method of producing openings in a shell of a dosage form
according to the invention using grinding means.
Figure 15 depicts a method of producing openings in a shell of a dosage form
according to the invention using hot pins.
Figure 16 depicts a method of producing openings in a shell of a dosage form
according to the invention using punching means.
As used herein, the term "dosage form" applies to any solid object, semi-solid,
or liquid composition designed to contain a specific predetermined amount (dose) of
a certain ingredient, for example an active ingredient as defined below. Suitable
dosage forms may be pharmaceutical drug delivery systems, including those for oral
administration, buccal administration, rectal administration, topical or mucosal
delivery, or subcutaneous implants, or other implanted drug delivery systems; or
compositions for delivering minerals, vitamins and other nutraceuticals, oral care
agents, flavorants, and the like. Preferably the dosage forms of the present invention
are considered to be solid, however they may contain liquid or semi-solid
components. In a particularly preferred embodiment, the dosage form is an orally
administered system for delivering a pharmaceutical active ingredient to the gastro-
intestinal tract of a human.
Suitable active ingredients for use in this invention include for example
Pharmaceuticals, minerals, vitamins and other nutraceuticals, oral care agents,
flavorants and mixtures thereof. Suitable Pharmaceuticals include analgesics, anti-
inflammatory agents, antiarthritics, anesthetics, antihistamines, antitussives,
antibiotics, anti-infective agents, antivirals, anticoagulants, antidepressants,
antidiabetic agents, antiemetics, antiflatulents, antifungals, antispasmodics, appetite
suppressants, bronchodilators, cardiovascular agents, central nervous system agents,
central nervous system stimulants, decongestants, oral contraceptives, diuretics,
expectorants, gastrointestinal agents, migraine preparations, motion sickness products,
mucolytics, muscle relaxants, osteoporosis preparations, polydimethylsiloxanes,
respiratory agents, sleep-aids, urinary tract agents and mixtures thereof.
the coated solid dosage form as measured by conventional pharmaceutical hardness
testing equipment, such as a Schleuniger Hardness Tester. In order to compare values
across different size tablets, the breaking strength must be normalized for the area of
the break. This normalized value, expressed in kp/cm2, is sometimes referred in the
art as tablet tensile strength. A general discussion of tablet hardness testing is found
in Leiberman et al., Pharmaceutical Dosage Forms - Tablets, Volume 2,2nd ed.,
Marcel Dekker Inc., 1990, pp. 213 - 217, 327 - 329.
The core may have one of a variety of different shapes. For example, the core
may be shaped as a polyhedron, such as a cube, pyramid, prism, or the like; or may
have the geometry of a space figure with some non-flat faces, such as a cone,
truncated cone, cylinder, sphere, torus, or the like. In certain embodiments, a core has
one or more major faces. For example, in embodiments wherein a core is a
compressed tablet, the core surface typically has two opposing major faces formed by
contact with the upper and lower punch faces in the compression machine. In such
embodiments the core surface typically further comprises a "belly-band" located
between the two major faces, and formed by contact with the die walls in the
compression machine. A core may also comprise a multilayer tablet.
Exemplary core shapes that may be employed include tablet shapes formed
from compression tooling shapes described by "The Elizabeth Companies Tablet
Design Training Manual" (Elizabeth Carbide Die Co., Inc., p. 7 (McKeesport, Pa.)
(incorporated herein by reference) as follows (the tablet shape corresponds inversely
to the shape of the compression tooling):
1. Shallow Concave.
2. Standard Concave.
3. Deep Concave.
4. Extra Deep Concave.
5. Modified Ball Concave.
6. Standard Concave Bisect.
7. Standard Concave Double Bisect.
8. Standard Concave European Bisect.
9. Standard Concave Partial Bisect.
10. Double Radius.
11. Bevel & Concave.
12. Flat Plain.
percent, e.g. at least about 70 weight percent, say at least about 80 weight percent
(based on the weight of the core) of one or more active ingredients.
The active ingredient or ingredients may be present in the dosage form in any
form. For example, the active ingredient may be dispersed at the molecular level, e.g.
melted or dissolved, within the dosage form, or may be in the form of particles, which
in turn may be coated or uncoated. If the active ingredient is in form of particles, the
particles (whether coated or uncoated) typically have an average particle size of about
1-2000 microns. In one preferred embodiment, such particles are crystals having an
average particle size of about 1-300 microns. In another preferred embodiment, the
particles are granules or pellets having an average particle size of about 50-2000
microns, preferably about 50-1000 microns, most preferably about 100-800 microns.
The core may be any solid form. The core may prepared by any suitable
method, including for example compression or molding. As used herein, "core" refers
to a material which is at least partially enveloped or surrounded by another material.
Preferably, the core is a self-contained unitary object, such as a tablet or capsule.
Typically, the core comprises a solid, for example, the core may be a compressed or
molded tablet, hard or soft capsule, suppository, or a confectionery form such as a
lozenge, nougat, caramel, fondant, or fat based composition. In certain other
embodiments, the core or a portion thereof may be in the form of a semi-solid or a
liquid in the finished dosage form. For example the core may comprise a liquid filled
capsule, or a semisolid fondant material. In embodiments in which the core
comprises a flowable component, such as a plurality of granules or particles, or a
liquid, the core preferrably additionally comprises an enveloping component, such as
a capsule shell, or a coating, for containing the flowable material. In certain particular
embodiments in which the core comprises an enveloping component, the shell or shell
portions of the present invention are in direct contact with the enveloping component
of the core, which separates the shell from the flowable component of the core.
In one embodiment the core is a compressed tablet having a hardness from
about 2 to about 30 kp/cm2, e.g. from about 6 to about 25 kp/cm2. "Hardness" is a
term used in the art to describe the diametral breaking strength of either the core or
13. Flat-Faced-Beveled Edge (F.F.B.E.).
14. F.F.B.E. Bisect.
15. F.F.B.E. Double Bisect.
16. Ring.
17. Dimple.
18. Ellipse.
19. Oval.
20. Capsule.
21. Rectangle.
22. Square.
23. Triangle.
24. Hexagon.
25. Pentagon.
26. Octagon.
27. Diamond.
28. Arrowhead.
29. Bullet.
30. Shallow Concave.
31. Standard Concave.
32. Deep Concave.
33. Extra Deep Concave.
34. Modified Ball Concave.
35. Standard Concave Bisect.
36. Standard Concave Double Bisect.
37. Standard Concave European Bisect.
38. Standard Concave Partial Bisect.
39. Double Radius.
40. Bevel & Concave.
41. Flat Plain.
42. Flat-Faced-Beveled Edge (F.F.B.E.).
43. F.F.B.E. Bisect.
44. F.F.B.E. Double Bisect.
45. Ring.
46. Dimple.
47. Ellipse.
48. Oval.
49. Capsule.
50. Rectangle.
51. Square.
52. Triangle.
53. Hexagon.
54. Pentagon.
55. Octagon.
56. Diamond.
57. Arrowhead.
58. Bullet.
59. Barrel.
60. HalfMoon.
61. Shield.
62. Heart.
63. Almond.
64. House/Home Plate.
65. Parallelogram.
66. Trapezoid.
67. Figure 8/Bar Bell.
68. Bow Tie.
69. Uneven Triangle.
The core typically comprises active ingredient and a variety of excipients,
depending on the method by which it is made.
In embodiments in which the core is made by compression, suitable excipients
include fillers, binders, disintegrants, lubricants, glidants, and the like, as known in
the art. In embodiments in which the core is made by compression and additionally
confers modified release of an active ingredient contained therein, such core
preferably further comprises a release-modifying compressible excipient.
Suitable fillers for use in making the core by compression include water-
soluble compressible carbohydrates such as sugars, which include dextrose, sucrose,
maltose, and lactose, sugar-alcohols, which include mannitol, sorbitol, maltitol,
xylitol, starch hydrolysates, which include dextrins, and maltodextrins, and the like,
water insoluble plastically deforming materials such as microcrystalline cellulose or
other cellulosic derivatives, water-insoluble brittle fracture materials such as
dicalcium phosphate, tricalcium phosphate and the like and mixtures thereof.
Suitable binders for making the core by compression include dry binders such
as polyvinyl pyrrolidone, hydroxypropylmethylcellulose, and the like; wet binders
such as water-soluble polymers, including hydrocolloids such as acacia, alginates,
agar, guar gum, locust bean, carrageenan, carboxymethylcellulose, tara, gum arabic,
tragacanth, pectin, xanthan, gellan, gelatin, maltodextrin, galactomannan, pusstulan,
laminarin, scleroglucan, inulin, whelan, rhamsan, zooglan, methylan, chitin,
cyclodextrin, chitosan, polyvinyl pyrrolidone, cellulosics, sucrose, starches, and the
like; and derivatives and mixtures thereof.
Suitable disintegrants for making the core by compression, include sodium
starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked
carboxymethylcellulose, starches, microcrystalline cellulose, and the like.
Suitable lubricants for making the core by compression include long chain
fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glycerides
and waxes.
Suitable glidants for making the core by compression, include colloidal silicon
dioxide, and the like.
In certain embodiments, the core or a portion thereof may optionally comprise
release modifying excipients as known in the art, for example as disclosed in
commonly assigned, copending U.S. Application Serial No._________[MCP 321],
the disclosure of which is incorporated by reference herein. Suitable release-
modifying compressible excipients for making the core by compression include
swellable erodible hydrophillic materials, insoluble edible materials, pH-dependent
polymers, and the like.
Suitable pharmaceutically acceptable adjuvants for making the cores by
compression include, preservatives; high intensity sweeteners such as aspartame,
acesulfame potassium, sucralose, and saccharin; flavorants; colorants; antioxidants;
surfactants; wetting agents; and the like and mixtures thereof.
In embodiments wherein one or more cores are prepared by compression, a
dry blending (i.e. direct compression), or wet granulation process may be employed,
as known in the art. In a dry blending (direct compression) method, the active
ingredient or ingredients, together with the excipients, are blended in a suitable
blender, than transferred directly to a compression machine for pressing into tablets.
In a wet granulation method, the active ingredient or ingredients, appropriate
excipients, and a solution or dispersion of a wet binder (e.g. an aqueous cooked starch
paste, or solution of polyvinyl pyrrolidone) are mixed and granulated. Alternatively a
dry binder may be included among the excipients, and the mixture may be granulated
with water or other suitable solvent. Suitable apparatuses for wet granulation are
known in the art, including low shear, e.g. planetary mixers; high shear mixers; and
fluid beds, including rotary fluid beds. The resulting granulated material is dried, and
optionally dry-blended with further ingredients, e.g. adjuvants and/or excipients such
as for example lubricants, colorants, and the like. The final dry blend is then suitable
for compression. Methods for direct compression and wet granulation processes are
known in the art, and are described in detail in, for example, Lachman, et al., The
Theory and Practice of Industrial Pharmacy. Chapter 11 (3rd ed. 1986).
The dry-blended, or wet granulated, powder mixture is typically compacted
into tablets using a rotary compression machine as known in the art, such as for
example those commercially available from Fette America Inc., Rockaway, NJ, or
Manesty Machines LTD, Liverpool, UK. In a rotary compression machine, a metered
volume of powder is filled into a die cavity, which rotates as part of a "die table" from
the filling position to a compaction position where the powder is compacted between
an upper and a lower punch to an ejection position where the resulting tablet is pushed
from the die cavity by the lower punch and guided to an ejection chute by a stationary
"take-off bar.
In one optional embodiment, the core may be prepared by the compression
methods and apparatus described in copending U.S. Patent Application Serial No.
09/966,509, pages 16-27, the disclosure of which is incorporated herein by reference.
Specifically, the core is made using a rotary compression module comprising a fill
zone, insertion zone, compression zone, ejection zone, and purge zone in a single
apparatus having a double row die construction as shown in Figure 6 of U.S. patent
application Serial No. 09/966,509. The dies of the compression module are
preferably rilled using the assistance of a vacuum, with filters located in or near each
die.
Cores made by compression may be single or multi-layer, for example bi-
layer, tablets.
The cores have a density of at least about 0.9 g/cc, e.g. at least about 1.0 g/cc.
Exemplary cores include a 385 mg compressed soft tablet with a volume of 0.4 cubic
centimeters, and a 586mg compressed tablet with a volume of about 0.5 cc.
A shell surrounds the cores. The shell comprises one or more openings
therein. The opening or openings provide a passageway for communication between
the core and the exterior of the dosage form. The openings may extend completely
through the thickness of the shell to contact the core, or only partially through the
shell.
The shell may be substantially unitary and continuous with the exception of
the openings therein, or the shell may comprise multiple portions, e.g. a first shell
portion and a second shell portion. In certain embodiments the shell or shell portions
are in direct contact with the core. In certain other embodiments, the shell or shell
portions are in direct contact with a subcoating which substantially surrounds the
core. In embodiments in which the shell comprises a first and second shell portion, at
least a first shell portion comprises openings therein.
In certain embodiments the first shell portion and second shell portion are
compositionally different. As used herein, the term "compositionally different"
means having features that are readily distinguishable by qualitative or quantitative
chemical analysis, physical testing, or visual observation. For example, the first and
second shell portions may contain different ingredients, or different levels of the same
ingredients, or the first and second shell portions may have different physical or
chemical properties, different functional properties, or be visually distinct. Examples
of physical or chemical properties that may be different include hydrophylicity,
hydrophobicity, hygroscopicity, elasticity, plasticity, tensile strength, crystallinity,
and density. Examples of functional properties which may be different include rate
and/or extent of dissolution of the material itself or of an active ingredient therefrom,
rate of disintegration of the material, permeability to active ingredients, permeability
to water or aqueous media, and the like. Examples of visual distinctions include size,
shape, topography, or other geometric features, color, hue, opacity, and gloss.
In one embodiment, the dosage form of the invention comprises: a) a core
containing an active ingredient; b) an optional subcoating that substantially covers the
core; and c) a shell comprising first and second shell portions residing on the surface
of the subcoating, the first shell portion comprising one.or more openings, and the
first shell portion being readily soluble in gastrointestinal fluids. As used herein,
"substantially covers" shall mean at least about 95 percent of the surface area of the
core is covered by the subcoating.
The use of subcoatings is well known in the art and disclosed in, for example,
United States Patent Nos. 3,185,626, which is incorporated by reference herein. Any
composition suitable for film-coating a tablet may be used as a subcoating according
to the present invention. Examples of suitable subcoatings are disclosed in United
States Patent Nos. 4,683,256,4,543,370,4,643,894,4,828,841,4,725,441,4,802,924,
5,630,871, and 6,274,162, which are all incorporated by reference herein.
Additional suitable subcoatings include one or more of the following ingredients:
cellulose ethers such as hydroxypropylmethyicellulose, hydroxypropylcellulose, and
hydroxyethylcellulose; polycarbohydrates such as xanthan gum, starch, and
maltodextrin; plasticizers including for example, glycerin, polyethylene glycol,
propylene glycol, dibutyl sebecate, triethyl citrate, vegetable oils such as castor oil,
surfactants such as polysorbate-80, sodium lauryl sulfate and dioctyl-sodium
sulfosuccinate; polycarbohydrates, pigments, and opacifiers.
In one embodiment, the subcoating comprises from about 2 percent to about 8
percent, e.g. from about 4 percent to about 6 percent of a water-soluble cellulose ether
and from about 0.1 percent to about 1 percent, castor oil, as disclosed in detail in
United States Patent No. 5,658,589, which is incorporated by reference herein. In
another embodiment, the subcoating comprises from about 20 percent to about 50
percent, e.g., from about 25 percent to about 40 percent of HPMC; from about 45
percent to about 75 percent, e.g., from about 50 percent to about 70 percent of
maltodextrin; and from about 1 percent to about 10 percent, e.g., from about 5 percent
to about 10 percent of PEG 400.
The dried subcoating typically is present in an amount, based upon the dry
weight of the core, from about 0 percent to about 5 percent.
Figure 1 depicts a dosage form 1 according to the invention comprising a shell
3 having a plurality of openings 2. Openings 2 are shaped as elongated slits, and do
not extend all the way through the shell 3 to the core (not shown) under the shell 3.
Figure 2 depicts another dosage form according to the invention. The dosage
form 1 comprises a core (not shown) covered a shell made of a first shell portion 3 a
and a second shell portion 3b. Shell portion 3a contains a plurality of openings 2a,
2b. Openings 2a are in the shape of dimples, while openings 2b are in the shape of
letters.
Figure 3 illustrates another dosage form according to the invention. Dosage
form 1 comprises a core (not shown) covered by a shell 3, which comprises openings
2a, 2b. Openings 2a are in the shape of circular holes, while openings 2b are in the
shape of letters.
Figure 4 shows another dosage form according to the invention. Dosage form
1 comprises a core 4 surrounded by a shell 3 having openings 2. Core 4 is partially
visible at the base of each opening 2 in shell 3.
Figure 5 depicts a further dosage form according to the invention. Dosage
form 1 comprises a football-shaped core (not shown) covered by a shell comprising a
first shell portion 3a and a second shell portion 3b. First shell portion 3a comprises a
plurality of small, round openings 2.
Each opening may have dimensions, e.g., length, width, or diameter, in the
range of about 0.1% to about 100%, of the diameter of the dosage form, or of any
dimension (e.g. diameter, length, or width) of a major face of the dosage form. The
diameter or width of each opening is preferably from about 0.5% to about 5% of the
diameter of the dosage form, or of any dimension (e.g. diameter, length, or width) of a
major face of the dosage form. In certain embodiments the diameter or width of the
openings may range from about 200 to about 2000 microns. The length of the
openings may range from about 1% to about 100% of the diameter of the dosage
form, or of the diameter of a major face of the dosage form. In certain particular
embodiments, the length or diameter of a major face of the dosage form is from about
10,000 to about 20,000 microns. In one particular embodiment, the length of the
openings is from about 100 to about 20,000 microns. The depth of the openings is
typically from about 75% to about 100% of the thickness of the shell at the location of
the openings. In certain embodiments, the thickness of the shell at the location of the
openings typically ranges from about 20 to about 800 microns, e.g. from about 100 to
about 400 microns. In one particular embodiment, the depth of the openings is from
about 75 to about 400 microns. If a plurality of openings are present, they are
typically spaced from one another by at least about one half, e.g. at least about one,
times the smallest dimension of the smallest opening. The openings may have a
variety of shapes, or be arranged in a variety of different patterns, and may have
similar or different sizes, such as depicted in Figure 6.
In one embodiment, the size of the openings is small enough to prevent the
core from being tasted, yet the number of openings is large enough to provide
communication between a certain percentage of surface area of the core and the
exterior of the dosage form.
The shell thickness at various locations maybe measured using a microscope,
for example, an environmental scanning electron microscope, model XL 30 ESEM
LaB6, Philips Electronic Instruments Company, Mahwah, WI. The shell thickness is
measured at 6 different locations on a single dosage form. The relative standard
deviation (RSD) is calculated as the sample standard deviation, devided by the mean,
times 100 as known in the art (i.e. the RSD is the standard deviation expressed as a
percentage of the mean). The RSD in shell thickness provides an indication of the
variation in the thickness of the shell on a single dosage form. In certain optional
embodiments of the invention, the relative standard deviation in shell thickness is less
than about 40%, e.g less than about 30%, or less than about 20%.
The dosage forms of the invention provide immediate release of one or more
active ingredients contained therein. The active ingredient or ingredients may be
found within the core, the shell, or portions or combinations thereof. In one
embodiment, at least one active ingredient is contained in the core.
In embodiments in which it is desired for the active ingredient to be absorbed
into the systemic circulation of an animal, the active ingredient or ingredients are
preferably capable of dissolution upon contact with a fluid such as water, gastric fluid,
intestinal fluid or the like. In one embodiment, the dissolution characteristics of at
least one active ingredient meets USP specifications for immediate release tablets
containing the active ingredient. For example, for acetaminophen tablets, USP 24
specifies that in pH 5.8 phosphate buffer, using USP apparatus 2 (paddles) at 50 rpm,
at least 80% of the acetaminophen contained in the dosage form is released therefrom
within 30 minutes after dosing, and for ibuprofen tablets, USP 24 specifies that in pH
7.2 phosphate buffer, using USP apparatus 2 (paddles) at 50 rpm, at least 80% of the
ibuprofen contained in the dosage form is released therefrom within 60 minutes after
dosing. See USP 24, 2000 Version, 19 - 20 and 856 (1999). In another embodiment,
at least about 70% the active ingredient can be detected in a suitable dissolution
medium after 60 minutes of stirring at suitable conditions.
Accordingly, the shell, or a portion thereof, is readily soluble in
gastrointestinal fluids. In a preferred embodiment in which the shell comprises a first
and second shell portion, at least the first shell portion comprises openings therein,
and is readily soluble in gastrointestinal fluids. In such embodiments, such shell or
shell portion will preferably be breached or dissolved within 30 minutes in 900 ml
water or 0.1 N HC1, or phosphate buffer solution at 37°C with stirring by a USP type
2 dissolution apparatus (Paddle method) at 50 or 100 rpm.
The shell or shell portion preferably comprises materials which exhibit rapid
dissolution in gastro-intestinal fluids. For example, such shell or shell portion may
comprise readily soluble materials selected from water soluble or water swellable film
formers, water soluble or water swellable thickeners, crystallizable and non-
crystallizable carbohydrates. In certain such embodiments, suitable water soluble or
water swellable film formers may be selected from water swellable cellulose
derivatives, thermoplastic starches, polyalkalene glycols, polyalkalene oxides, and
amorphous sugar glass, and combinations thereof. In certain other such embodiments,
suitable film formers may be selected from film forming water soluble polymers such
as for example water soluble vinyl polymers, water soluble polycarbohydrates, and
water soluble oopolymers; film-forming proteins, and combinations thereof. In
certain other such embodiments, suitable thickeners may be selected from gelling
polymers or hydrocolloids; gelling starches, and crystallizable carbohydrates. In
certain other such embodiments, suitable non-crystallizable carbohydrates may be
selected from polydextrose, starch hydrolysates, and non-crystallizable sugar
alcohols. In one embodiment, the shell preferably comprises at least about 50%,
preferably at least about 80%, most preferably at least about 90% of a material
selected from film formers, gelling polymers, low-melting hydrophobic materials,
non-crystallizable sugars or sugar alcohols, and mixtures thereof. In another
embodiment, the shell comprises at least about 50%, preferably at least about 80%,
most preferably at least about 90% of a material selected from film formers, gelling
polymers, low-melting hydrophobic materials, and mixtures thereof.
In another particular embodiment, the shell comprises less than about 50%,
preferably less than about 25%, most preferably less than about 5% of a crystallizable
sugar.
In another embodiment, the dosage form is substantially free (i.e. less than 1%
by weight, preferably less man about 0.1 % by weight, based upon the shell weight) of
charge control agents. As used herein, the term "charge control agents" refers to a
material having a charge control function, such as those used for electrostatic
deposition of coatings onto substrates. Such charge control agents include metal
salicylates, for example zinc salicylate, magnesium salicylate and calcium salicylate;
quaternary ammonium salts; benzalkonium chloride; benzethonium chloride;
trimethyl tetradecyl ammonium bromide (cetrimide); and cyclodextrins and their
adducts.
In certain optional embodiments, the shell itself or an outer coating thereon
may contain active ingredient. In one particular embodiment, such active ingredient
will be released immediately from the dosage form upon contact with suitable liquid
media. In another embodiment, the shell comprises a first shell portion and a second
shell portion. An outer coating resides upon the second shell portion, while the first
shell portion comprises openings therein. Active ingredient may be released either
immediately, or in a controlled, e.g. sustained, prolonged, extended manner, or in a
delayed, e.g. pulsatile, or repeat action manner from the dosage form upon contact
with suitable liquid media. In embodiments wherein the active ingredient is released
immediately from the outer coating, the outer coating is also preferably readily
soluble in gastrointestinal fluids, as described above.
The shell may be applied to the core by any suitable method, for example by
spraying, dipping, enrobing, or molding. Suitable spray-coating methods are
described in, for example, United States Patent Nos. 3,185,626,4,683,256,
4,543,370,4,643,894,4,828,841, 4,725,441,4,802,924, 5,630,871, and 6,274,162, the
disclosures of which are all incorporated by reference herein. Suitable dipping
methods are described in U.S. Patent Nos. 4,820,524, 5,538,125; 5,228,916;
5,436,026; 5,679,406, the disclosures of which are all incorporated by reference
herein. Suitable enrobing methods are described in U.S. Patent Nos. 5,146,730 and
5,459,983. Suitable molding methods are described herein.
In certain optional embodiments of the invention, the core, the shell, or both
are prepared by molding. In particular, the core, the shell, or both may be made by
solvent-based molding or solvent-free molding, In such embodiments, the core or the
shell is made from a flowable material optionally comprising active ingredient. The
flowable material may be any edible material that is flowable at a temperature
between about 37°C and 250°C, and that is solid, semi-solid, or can form a gel at a
temperature between about -10°C and about 35°C. When it is in the fluid or flowable
state, the flowable material may comprise a dissolved, dispersed, or molten
component, and optionally a solvent such as for example water or organic solvents, or
combinations thereof. The solvent may be partially or substantially removed by
drying.
In one embodiment, solvent-based or solvent-free molding is performed via
thermal setting molding using the method and apparatus described in copending U.S.
patent application Serial No. 09/966,450, pages 57-63, the disclosure of which is
incorporated herein by reference, In this embodiment, a core or shell is formed by
injecting flowable form into a molding chamber. The flowable material preferably
comprises a thermal setting material at a temperature above its melting point but
below the decomposition temperature of any active ingredient contained therein. The
starting material is cooled and solidifies in the molding chamber into a shaped form
(i.e., having the shape of the mold).
According to this method, the flowable material may comprise solid particles
suspended in a molten matrix, for example a polymer matrix. The flowable material
may be completely molten or in the form of a paste. The flowable material may
comprise an active ingredient dissolved in a molten material. The flowable material
may comprise solid particles dispersed in a fluid carrier. Alternatively, the flowable
material may be made by dissolving a solid in a solvent, which solvent is then
evaporated after the molding step.
In another embodiment, solvent-based or solvent-free molding is performed by
thermal cycle molding using the method and apparatus described in copending U.S.
patent application Serial No. 09/966,497, pages 27-51, the disclosure of which is
incorporated herein by reference. Thermal cycle molding is performed by injecting a
flowable material into a heated molding chamber. The flowable material may
comprise active ingredient and a thermoplastic material at a temperature above the set
temperature of the thermoplastic material but below the decomposition temperature of
active ingredient. The flowable material is cooled and solidifies in the molding
chamber into a shaped form (i.e., having the shape of the mold).
In the thermal cycle molding method and apparatus of U.S. patent application
Serial No. 09/966,497 a thermal cycle molding module having the general
configuration shown in Figure 3 therein is employed. The thermal cycle molding
module 200 comprises a rotor 202 around which a plurality of mold units 204 are
disposed. The thermal cycle molding module includes a reservoir 206 (see Figure 4)
for holding flowable material. In addition, the thermal cycle molding module is
provided with a temperature control system for rapidly heating and cooling the mold
units. Figures 55 and 56 depict the temperature control system 600.
The mold units may comprise center mold assemblies 212, upper mold
assemblies 214, and lower mold assemblies 210, as shown in. Figures 26-28, which
mate to form mold cavities having a desired shape, for instance of a core or a shell
surrounding one or more cores. As rotor 202 rotates, opposing center and upper mold
assemblies or opposing center and lower mold assemblies close. Flowable material,
which is heated to a flowable state in reservoir 206, is injected into the resulting mold
cavities. The temperature of the flowable material is then decreased, hardening the
flowable material. The mold assemblies open and eject the finished product.
In one optional embodiment of the invention, the shell is applied to the dosage
form using a thermal cycle molding apparatus of the general type shown in Figures
28A-C of copending U.S. Application Serial No. 09/966,497 comprising rotatable
center mold assemblies 212, lower mold assemblies 210 and upper mold assemblies
214. Cores are continuously fed to the mold assemblies. Shell flowable material,
which is heated to a flowable state in reservoir 206, is injected into the mold cavities
created by the closed mold assemblies holding the cores. The temperature of the shell
flowable material is then decreased, hardening it around the cores. The mold
assemblies open and eject the finished dosage forms. Shell coating is performed in
two steps, each half of the dosage forms being coated separately as shown in the flow
diagram of Figure 28B of copending U.S. Application Serial No. 09/966,939 via
rotation of the center mold assembly.
In one embodiment, the compression module of copending U.S. patent
application Serial No. 09/966,509, pp. 16-27 may be employed to make the core and
the shell is applied to the core using a thermal cycle molding module as described
above. A transfer device as described in U.S. patent application Serial No.
09/966,414, pp. 51-57, the disclosure of which is incorporated herein by reference,
may be used to transfer the cores from the compression module to the thermal cycle
molding module. Such a transfer device may have the structure shown as 300 in
Figure 3 of copending U.S. Application Serial No. 09/966,939. It comprises a
plurality of transfer units 304 attached in cantilever fashion to a belt 312 as shown in
Figures 68 and 69 of copending U.S. Application Serial No. 09/966,939. The transfer
device rotates and operates in sync with the compression module and the thermal
cycle molding module to which it is coupled. Transfer units 304 comprise retainers
330 for holding cores as they travel around the transfer device.
Suitable thermoplastic materials for use in or as the flowable material include
both water soluble and water insoluble polymers that are generally linear, not
crosslinked, and not strongly hydrogen bonded to adjacent polymer chains. The
thermoplastic material may be single materials, or may be mixtures of materials with
solvent or plasticizer. Examples of suitable thermoplastic materials include those
comprising water swellable cellulose derivatives, water insoluble cellulose
derivatrives, thermoplastic vinyl polymers, thermoplastic starches, thermoplastic
polyalkalene glycols, thermoplastic polyalkalene oxides, and amorphous sugar-glass,
and the like, and derivatives, copolymers, and combinations thereof. Examples of
suitable thermoplastic water swellable cellulose derivatives include hydroxypropyl
cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC),
and their combinations with water or other suitable solvents and/or plasticizers.
Examples of suitable thermoplastic water insoluble cellulose derivatives include
cellulose acetate (CA), ethyl cellulose (EC), cellulose acetate butyrate (CAB),
cellulose propionate, and their combinations with suitable organic solvents and/or
plasticizers. Examples of suitable thermoplastic vinyl polymers include polyvinyl
alcohol (PVA) and polyvinyl pyrrolidone (PVP). Examples of suitable thermoplastic
starches are disclosed for example in U.S. Patent No. 5,427,614. Examples of
suitable thermoplastic polyalkalene glycols include polyethylene glycol. Examples of
suitable thermoplastic polyalkalene oxides include polyethylene oxide having a
molecular weight from about 100,000 to about 900,000 Daltons. Other suitable
thermoplastic materials include sugar in the form on an amorphous glass such as that
used to make hard candy forms.
It should be noted that, when used to make the shell, the flowable material
must be a material readily soluble in gastrointestinal fluids, as described above.
In those embodiments in which the shell is prepared using a solvent-free
molding process, the shell typically comprises at least about 30 percent, e.g. at least
about 45 percent by weight of a thermal-reversible carrier. .The shell may optionally
further comprise up to about 30 weight percent total of various plasticizers, adjuvants
and excipients.
In those embodiments in which the shell is prepared using a solvent-based
molding process, the shell typically comprises at least about 10 weight percent, e.g. at
least about 12 weight percent or at least about 15 weight percent or at least about 20
(PVP). Examples of suitable thermoplastic starches for use as thermal-reversible
carriers are disclosed for example in U.S. Patent No. 5,427,614. Examples of suitable
thermoplastic resins for use as themal-reversible carriers include dammars, mastic,
rosin, shellac, sandarac, and glcerol ester of rosin. In one embodiment, the thermal-
reversible carrier for making a core by molding is selected from polyalkylene glycols,
polyalkaline oxides, and combinations thereof.
In embodiments in which the shell comprises an active ingredient intended to
have immediate release from the dosage form, the shell is preferably prepared via
solvent-free molding. In such embodiments a thermal-reversible carrier is employed
in the flowable material to make the shell, said thermal-reversible carrier preferably
selected from polyethylene glycol with weight average molecular weight from about
1450 to about 20000, polyethylene oxide with weight average molecular weight from
about 100,000 to about 900,000, and the like.
In a preferred embodiment of the invention, the shell is applied to the core by
enrobing. In enrobing methods, cast films are applied to opposite sides of a core, i.e.,
a compressed tablet, using rotating dies, and are sealed together in an essentially
edge-to-edge manner at a seal line that extends around the core at a desired place.
The dies are positioned such that the surfaces are in abutting relationship with one
another, thereby forming a nip in between. Each of the dies has a series of matching
recesses on its circumferential surface. As the dies rotate, the films are joined and
fused together at the nip between the dies where a pair of matching recesses form a
pocket into which a core is dropped by a metered feed mechanism. As the dies
continue to rotate, the core urges the films into the interior of the recesses in the dies,
and the core is thereby securely enveloped and enrobed by the films, while the films
continue to be joined about the core by the dies. Simultaneously with the fusing of
the films about the core, the enrobed core is pinch cut from the films by the rotary
dies, whereupon it separates from the films in the form of an individual enrobed
dosage form.
Useful enrobing methods and apparatuses are described for example in U.S.
Patent Nos. 5,146,730 and 5,459,983, the disclosures of which are incorporated herein
weight percent or at least about 25 weight percent of a film-former. The shell may
again also optionally further comprise up to about 30 weight percent total of various
plasticizers, adjuvants, and excipients.
The total weight of the shell is preferably about 20 percent to about 400
percent of the total weight of the cores. In embodiments wherein the shell is prepared
by a solvent-free molding process, the total weight of the shell is typically from about
50 percent to about 400 percent, e.g. from about 75 percent to about 400 percent, or
about 100 percent to about 200 percent of the total weight of the cores. In
embodiments wherein the shell is prepared by a solvent-based molding process, the
total weight of the shell is typically from about 20 percent to about 100 percent of the
total weight of the cores.
In embodiments in which the shell is applied to the core by molding, at least a
portion of the shell surrounds the core such that the shell inner surface resides
substantially confonnally upon the core outer surface. As used herein, the term
"substantially conformally" shall mean that the inner surface of the shell has peaks
and valleys or indentations and protrusions corresponding substantially inversely to
the peaks and valleys of the outer surface of the core, hi certain such embodiments,
the indentations and protrusions typically have a length, width, height or depth in one
dimension of greater than 10 microns, say greater than 20 microns, and less than
about 30,000 microns, preferably less than about 2000 microns.
m those embodiments in which solvent-free molding is employed, the
flowable material may comprise a thermal-reversible carrier. Suitable thermal-
reversible carriers for use in making a core, the shell or both by molding are
thermoplastic materials typically having a melting point below about 110°C, more
preferably between about 20 and about 100°C. Examples of suitable thermal-
reversible carriers for solvent-free molding include thermplastic polyalkalene glycols,
thermoplastic polyalkalene oxides, low melting hydrophobic materials, thermoplastic
polymers, thermoplastic starches, and the like. Preferred thermal-reversible carriers
include polyethylene glycol and polyethylene oxide. Suitable thermoplastic
polyalkylene glycols for use as thermal-reversible carriers include polyethylene glycol
having molecular weight from about 100 to about 20,000, e.g. from about 100 to
about 8,000 Daltons. Suitable thermoplastic polyalkalene oxides include
polyethylene oxide having a molecular weight from about 100,000 to about 900,000
Daltons. Suitable low-melting hydrophobic materials for use as thermal-reversible
carriers include fats, fatty acid esters, phospholipids, and waxes which are solid at
room temperature, fat-containing mixtures such as chocolate; and the tike. Examples
of suitable fats include hydrogenated vegetable oils such as for example cocoa butter,
hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenated sunflower
oil, and hydrogenated soybean oil; and free fatty acids and their salts. Examples of
suitable fatty acid esters include sucrose fatty acid esters, mono, di, and triglycerides,
glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl
tristearate, glyceryl trilaurylate, glyceryl myristate, GlycoWax-932, lauroyl macrogol-
32 glycerides, and stearoyl macrogol-32 glycerides. Examples of suitable
phospholipids include phosphotidyl choline, phosphotidyl serene, phosphotidyl
enositol, and phosphotidic acid. Examples of suitable waxes which are solid at room
temperature include carnauba wax, spermaceti wax, beeswax, candelilla wax, shellac
wax, microcrystalline wax, and paraffin wax. Suitable thermoplastic polymers for use
as thermal-reversible carriers include thermoplastic water swellable cellulose
derivatives, thermoplastic water insoluble polymers, thermoplastic vinyl polymers,
thermoplastic starches, and thermoplastic resins, and combinations thereof. Suitable
thermoplastic water swellable cellulose derivatives include include
hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC),
carboxymethylcellulose (CMC), cross-linked hydroxypropylcellulose, hydroxypropyl
cellulose (HPC), hydroxybutylcellulose (HBC), hydroxyethylcellulose (HEC),
hydroxypropylethylcellulose, hydroxypropylbutylcellulose,
hydroxypropylethylcellulose, and salts, derivatives, copolymers, and combinations
thereof. Suitable thermoplastic water insoluble polymers include ethylcellulose,
polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose acetate and its
derivatives, acrylates, methacrylates, acrylic acid copolymers, and the like and
derivatives, copolymers, and combinations thereof. Suitable thermoplastic vinyl
polymers include polyvinylacetate, polyvinyl alcohol, and polyvinyl pyrrolidone
by reference. Referring to the 730 patent and Figure 13 in particular, cast films 36
and 37 are formed on rotating casting drums 42 and 43, which are cooled by a
coolant. The films are fed through a series of rotating drums to drum-like dies 38 and
39, which rotate synchronously with one another. Dies 38 and 39 are symmetrically
disposed relative to one another about a functional center plane 54 of the overall
enrobing apparatus. Films 36 and 37 contact each other at the nip between dies 38
and 39. Here, the cores are enrobed with coating, and the two films are sealed
together and cut.
Specifically, a web is created as films 36 and 37 converge and are squeezed
together. The films self-adhere together. After emerging from between dies 38 and
39, the web containing the enrobed cores passes between a pair of mangle rolls 63.
The web is stretched, and the enrobed cores self separate and drop into product
receptacles 65.
Referring to Figure 20 of the '730 patent, each die 38,39 has a plurality of
recesses 108, which cooperate with corresponding recesses in the other die. The
cavities of these recesses are shaped to receive a single core. The cavities are defined
by ribs 109 that close together to cut the enrobed cores from the web. Teem 115 on
the edges of the dies 38,39 grip the films 36,37.
The enrobed cores can be washed and dried, and optionally further processed
as desired.
In another embodiment, the shell is again applied to the core by enrobing,
however the films used to make the shell each comprise visually distinct portions, for
example stripes. The films are applied by the enrobing method described in
commonly assigned, copending U.S. Application Serial Nos.____________[MCP
301 and MCP3161. Referring generally to Figures 9-11 therein, the film casting
apparatus 30 for this method of enrobing comprises a casting drum 34, the exterior
surface 36 of which is cooled to at least partially solidify coating materials coming
into contact therewith. A multi-chamber slit extruder 38 deposits film onto the
casting drum 34. The extruder 38 comprises partitions 58,60,62 mat divide the
interior 44 into four chambers 64,66, 68, 70. The chambers 64,66,68, 70 can each
92b', 92c' of each film 32,32'. All of the color transitions 92a, 92b, 92c, 92a', 92b',
92c' are aligned with the conjugate plane of symmetry 16 of a corresponding core 10.
Furthermore, the enrobing apparatus 102 preferably includes registering
means 120 (shown schematically in Figure 14 of the [MCP 301]________-
application) for ensuring that the colored stripes (not shown) of the films 32,32' are
properly aligned with one another prior to passage between the rotary dies 112,112'.
The registering means 120 also ensures that the positions of the dispensed cores 10
are appropriate relative to the color transitions 92a, 92b, 92c, 92a', 92b', 92c', such
that the transition between the colors on the resulting products 122 are properly
matched with one another and the conjugate plane of symmetry 18 of each core 10.
An enlarged schematic perspective view of the drum-like rotary dies 112, 112'
is provided in Figure 16 of the [MCP 301]________application. The rotary dies
112,112' are substantially identical to one another, each having an exterior
circumferential surface 124,124' with a series of recesses 126,126' thereon. Each
recess 126,126' is arranged such that its length 130, 130' is aligned parallel to the
axis of rotation AR, AR' of its respective rotary die 112,112'. Each recess 126 on
one die 112 cooperates with a corresponding recess 126' on the other die 112'. In
addition, the number of rows of recesses 126,126' should correspond to the number
of color transitions 92a, 92b, 92c, 92a', 92b', 92c' between the stripes 84, 86, 88, 90,
84', 86', 88', 90' on the striped films 32, 32', respectively, mat pass between the dies
112,112'.
The orientation of the striped films 32, 32' as they pass between the rotary
dies 112,112' is such that, for example, red stripes 84, 88 of one film 32 are matched
with the red stripes 84', 88' of the other film 32' and yellow stripes 86, 90, 86', 90' of
each film 32,32', respectively, are similarly matched with one another. The
registering means 120 of the enrobing apparatus 102 may be used to facilitate the
orientation of the films 32,32' such that the matching and alignment of the color
transitions of each film are improved.
As the rotary dies 112,112' rotate, the cores 10 are dispensed to the nip
between the dies 112, 112' such that they are oriented with their lengths aligned
contain visually different coating materials, i.e., different colored coating materials.
Each partition has a tapered blade edge 94, 96, 98 to control the flow of coating
material onto the casting drum 34. The coating materials are supplied to the chambers
from for example feeder pipes 72, 74. An open slit 78 is located at the bottom of the
slit extruder 38. Slit 78 communicates with each chamber 64, 66,68, 70. The slit
extruder is heated to heat the coating materials to a flowable state, which depending
on the material may be in the range of about 40 to 250" C.
Referring to Figures 14-16 of the [MCP 301] application, an enrobing
apparatus 102 for use with cast films having visually distinct portions similar to that
described in U.S. Patent Nos. 5,146,730 and 5,459,983 may be used. In particular,
cast films 32,32' are moved in a continuous manner, by a series of rollers 106,108,
110,106', 108', 110' toward a pair ofcoacting rotary dies 112,112', which are
positioned symmetrically on either side of the central plane of symmetry 104 of the
apparatus 102. The rotary dies 112, 112' rotate on their axes of rotation AR, ARrespectively, thereby forming a nip in between. The nip between the rotary dies 112,
112' lies in the aforesaid central plane of.symmetry 104 and the striped films 32, 32'
are passed therethrough.
i The enrobing apparatus 102 also includes a core dispensing means 118, which
holds a supply of cores 10 and dispenses them to the nip in a timed manner. The core
dispensing means 118 is also aligned with the central plane of symmetry 104. The
core dispensing means 118 orients and dispenses each core 10 such mat the core 10
simultaneously contacts the contact surfaces 32a, 32a' of the converging striped films
32,32' as the core 10 enters the nip, with its transverse plane of symmetry 16 lying in
the central plane of symmetry 104 of the enrobing apparatus 102, and the color
transitions 92a, 92a' of the films 32, 32', respectively, lying in the conjugate plane of
symmetry 18 of the core 10. The films 32,32' are then stretched around the opposite
sides of each core 10 symmetrically.
Figure 15 of the [MCP 301]________application shows the proper
positioning of the cores 10 in between the striped films 32, 32' as they enter the nip
between the dies 112,112' and relative to the color transitions 92a, 92b, 92c, 92a',
parallel to the axes of rotation AR, AR' of the dies 112,112' and each core 10 is
thereby properly aligned to be received between a pair of coacting recesses 126, 126'.
The rotary dies 112,112' continue to rotate and the films 32, 32' are sealed to each
other by the raised rims 128,128' of the coacting recesses 126, 126', around the core
10 thereby forming a film seam 134, which lies in the transverse plane of symmetry
16 of the core 10. The raised rims 128,128' also cut through the bonded films 32,
32', at the film seam 134 around each enrobed core 10, thereby releasing the enrobed
core products 122, from the bonded films 32,32'.
The film seam 134 created may comprise abutting film edges. It is also
possible to have a film seam 134 wherein the cut edge of one film 32 slightly overlaps
the cut edge of the other film 32' by an amount approximately equal to the thickness
of the films 32,32'. Alternatively, the film seam 134 could be formed such that the
cut edges of the films 32, 32' are aligned with one another about the core 10, but are
spaced apart slightly by a distance that is approximately equal to the thickness of the
films 32, 32'.
If aesthetically desired, the films 32, 32' may be aligned such that the resulting
products 122 have a film seam 134 wherein a stripe of one color (for example, a red
stripe 84) (or visual distinction) of one film 32 abuts or overlaps a stripe of another
color (for example, a yellow stripe 90') (or visual distinction) of the other film 32' to
form a product 122 having a "checkerboard pattern", i.e., having four quadrants of
alternating red and yellow colors (or other visual distinctions).
Figures 17-19 of the [MCP 301]_________- application depict an
alternative film casting apparatus 136 for use with enrobing processes. The
alternative film casting apparatus 136 includes film receiving means, such as a
conventional metal casting belt 140 that is mounted onto two rotating drums 142,144,
for receiving the film 138 being cast thereon. The rotating drums 142,144 rotate,
thereby causing the casting belt 140 to move in the directions indicated by the arrows
J and K. A warming plate 148 may be positioned adjacent to the casting belt 140 to
warm the casting belt 140 prior to casting film thereon. A cooling plate 150 is
positioned adjacent to the casting belt 140 to cool the casting belt 140 after film is cast
thereon.
The alternative film casting apparatus 136 further includes film depositing
means, such as a reciprocating multi-chamber slit extruder 146, for depositing the film
138, in a semi-continuous manner, onto the casting belt 138. As with the slit extruder
38 discussed above, the reciprocating slit extruder 146 includes interior partitions 152,
154,156 that form interior chambers 158,160,162,164 for holding visually distinct
coating material 166,168 therein. A slit 170 is also provided, through which the
coating materials 166,168 flow out of the chambers 158,160,162,164 and onto the
casting belt 140, thereby creating a striped film 138.
The reciprocating slit extruder 146 also includes supply means, such as feeder
pipes 182,184 for supplying the coating materials 166, 168 to each of the chambers
158,160, 162,164 and flow control means, such as a slidable gate 180 for controlling
the flow of the coating materials 166,168 from the chambers 158,160,162,164.
Each of the interior partitions 152,154,156 of the reciprocating slit extruder 146 has
stripe control means, such as a tapered blade edge, to control the flow of the coating
materials 166,168 exiting the chambers 158,160,162, 164. One notable difference
between the slit extruder 38 described above and the present reciprocating slit
extruder 146 is that reciprocating slit extruder 146 is connected to a conventional
motor such that it moves reciprocatingly in the directions indicated by arrow M in
Figure 18 of the [MCP 301]________- application.
Initially, feeder pipes 182, 184 supply coating materials 166,168 of two
colors, such as red and yellow, respectively, to alternate chambers 158,160,162,164,
respectively, of the reciprocating slit extruder 146. Within chambers 158,160,162,
164 the coating materials 166,168 become or are maintained as liquid and flowable.
Cooling plate 150 at least partially solidifies the coating material 166,168 upon
physical contact with the surface of the casting belt 140 to form the transversely
striped film 138.
After the coating materials 166,168, the warming plate 148 and the cooling
plate 150 have attained their desired temperatures, a portion 198 of the casting belt
140 is warmed by the wanning plate 148 and is then advanced by the rotating drums
142,144 to a position underneath the reciprocating slit extruder 146. The slidable
gate 180 is men moved to a position which opens the slit 170 to the thickness that is
desired for the striped film 138. While the rotating drums 142,144 and the casting
belt 140 remain stationary, the coating materials 166, 168 flow out of the chambers
158,160,162,164, along the tapered blade edges (not shown), through the slit 170
and onto the warmed portion 198 of the casting belt 140, which briefly maintains the
coating material 166,168 in a substantially liquid, flowable state.
Simultaneously with the flow of the coating materials 166,168 onto the
casting belt 140, the reciprocating slit extruder 146 is moved from a first position 194
to a second position 196, where it is temporarily halted. As soon as the reciprocating
slit extruder 146 reaches its second position 196, the slidable gate 180 is moved to a
closed position, thereby blocking the slit 170 and temporarily halting the flow of
coating materials 166,168, which results in the formation of a film segment 200. The
film segment 200 has alternating, transversely oriented red stripes 172, 176 and
yellow stripes 174,178 with straight and consistent color transitions 186,188,190
therebetween.
Next, the casting belt 140 is moved by the rotating drums 142,144, such that
the film segment 200 is moved, and a newly warmed portion of the casting belt 140 is
positioned beneath the reciprocating slit extruder 140. The first film segment 200 is
cooled while the second film segment is cast onto the casting belt 140.
When it is desired to cast a subsequent film segment, with the reciprocating
slit extruder 146, now in its second position 196, and the casting belt 140 held
stationary, the slidable gate 180 is again moved to a position which opens the slit 170
by an amount that is equal to the thickness desired for the striped film 138. As
coating materials 166,168 flow out onto the casting belt 140, the reciprocating slit
extruder 146 is moved from its second position 196 back to its first position 194,
where it is again temporarily halted. As the coating materials 166,168 are being cast
onto the casting belt 140, the first edge of the new film segment will meet and bond
with the second edge 204 of the first film segment 200. After the reciprocating slit
extruder 146 returns to its first position 194, the slidable gate 180 is again moved to
its closed position, thereby blocking the slit 170 and temporarily halting the flow of
coating materials 166,168, which results in the creation of a new film segment that is
bonded to the first film segment 200.
The foregoing process steps are repeated continuously, resulting in a film
casting process that is semi-continuous and which produces a continuous ribbon of
transversely striped film 138. The transversely striped film 138 is continuously
removed from the casting belt 140 by a scraper or other device and then fed into the
rotary die enrobing apparatus 102 for enrobing cores 10 as described above.
However, because the alternative film casting apparatus 136 produces film 138 having
stripes that are transversely oriented, rotary dies 208,208' have recesses 210,210'
which are oriented such that their lengths are aligned perpendicularly to the axes of
rotation of their respective rotary dies. In addition, the core dispensing means used
herewith orients, and dispenses each core 10 to the nip between the dies 208,208' end-
first, i.e., such that one of the ends 12,14 of each caplet 10 simultaneously contacts
the converging films 138,138' as the core 10 enters the nip.
Figures 22-30 of the [MCP 301]_________application are directed to an
alternative enrobing apparatus for making films with visually distinct portions, which
includes the alternative film casting apparatus 136 described above. A transversely
striped film is fed, along with cores, into the alternative enrobing apparatus to produce
bi-colored products, each having a film seam that only partially circumscribes the
core and which lies in a reference plane that is different from the reference plane in
which the color transition of the product lies.
The alternative enrobing apparatus includes a conveyor system 220 that
comprises a series of horizontally-oriented rollers 222 and pairs of rollers, 224,226,
228 for supporting and conveying the transversely striped film 138. A core
dispensing means 230 is positioned above the conveyor system 220 and the film 138
for the purpose of dispensing cores 10 onto the film 138 in the required orientation
with respect to the color transitions 186,188,190. The core dispensing means 230
includes slat feeders 234,236 that orient the cores as required for proper positioning
onto the film 138. The core dispensing means 230 further includes a core positioning
slat 238 and a core plunger 240 positioned above the positioning slat 238.
Cores 10 are fed from hopper 232, through the slat feeders 234,236, to the
positioning slat 238. The cores 10', 10", 10'" are lined up, end 12 to end 14 and,
thereby, each core is moved along the positioning slat 238 in a substantially
continuous manner by the core behind it. When a core 10' is pushed beyond the
support rails 248, 250 and is no longer supported thereby, and when the position of a
color transition 186 of the film 138 lies in the conjugate plane of symmetry 18' of
core 10', a registering means 242 signals a motor, which moves the plunger 240 up
and down until the core 10' contacts and rests upon the film 138. When plunger 240
reaches its uppermost position, it momentarily stops until the next core 10" is moved
beyond support rails 248,250 contained within the positioning slat 238. The
foregoing events are repeated continuously as long as cores 10 are fed and moved
through the positioning slat 238.
The beginning portion of the conveyor system 220, i.e., the portion that is
located between the alternative film casting apparatus 136 and a short distance on the
opposite side of the core positioning slat 238, is comprised of horizontally-oriented
rollers 222. Film 138 is moved by the horizontally-oriented rollers 222 along this
beginning portion. The remaining portion of the conveyor system 220, which is
located between a short distance past the positioning slat 238 and the rotary dies 260,
262, is comprised of pairs of rollers 224,226,228. As shown schematically in Figure
26 of the [MCP 301]_________application, the individual rollers of sequential pairs
of rollers 224,226,228 are gradually and sequentially pivoted upward from the
horizontal plane, in increments of about 10 degrees for each successive pair of rollers
224,226,228, starting proximate to the positioning slat 238. Accordingly, as the film
138 approaches the rotary dies 260,262, the film 138 is folded longitudinally about
the cores 10.
The rotary dies 260,262 rotate and cooperate with one another to form a nip
therebetween, into which the cores 10 and the film 138 are fed. Likewise, each of the
dies 260,262 have recesses 282,284, arranged circumferentially in a row on the
surface of each die 260, 262. The recesses 282,284 each have raised rims for sealing
and cutting the bonded film 138 about the cores 10, thereby enrobing the cores 10.
The rotary dies 260,262 however, are oriented such that they rotate in the horizontal
plane, rather than in the vertical plane as do the previously discussed rotary dies 112,
112', 208,208'. Furthermore, when the cores 10 are fed into the nip, the film 138 is
folded and partially bonded about them. Furthermore, the partially enrobed cores 10
are fed successively, i.e., one-by-one, into the nip between the dies 260, 262.
The shell may also be applied to the core using a vacuum forming apparatus.
Commonly assigned, copending U.S. Patent Application Serial Nos. [MCP 301 and
MCP 316]________________disclose such apparatuses.
With reference to Figures 31-44 of the [MCP 301]______________
application, a vacuum forming apparatus 292 includes a first plurality of individual
porous platens 294, a first conveyor system 296 and a second conveyor system 298.
The first and second conveyor systems 296,298 are arranged in series with one
another, thereby creating a single path along which the porous platens 294 are moved
in semi-continuous fashion. The first and second conveyer systems 296,298 are
provided with conventional vacuum sources that apply a vacuum to each of the
porous platens 294 while they are moved along the apparatus.
The vacuum forming apparatus 292 further includes a second plurality of
individual porous platens 304 and a third conveyor system 306 that moves porous
platens 304 along a second path, which is shown by the arrow GG in Figure 31. The
third conveyor system 306 is positioned between the first and second conveyor
systems 296,298.
A rotating mechanism 308 is also positioned between the first and second
conveyor systems 296,298. The rotating mechanism 308 simultaneously holds
together two of platens, i.e., one platen 294 and a corresponding platen 304, and
rotates them together, such that the platen 304, first on top, is inverted and positioned
on the bottom.
Each porous platen 294,304 has at least one recess 310,312, respectively,
sized and shaped to temporarily but snugly receive therein a core 10 to be enrobed.
It is possible to achieve multi-colored enrobed products having color
transitions oriented in a variety of different ways using different combinations of the
platens with transversely and longitudinally striped films. However, within a
particular vacuum forming apparatus, the orientation of the recesses 310, 312 in all of
the platens 294,304 must be longitudinal, or, alternatively, me orientation of the
recesses 310,312 in all of the platens 294,304 must be transverse (or otherwise
aligned with the orientation of the stripes on the films).
The vacuum forming apparatus 292 further includes a first pair of rollers 338,
340 having a film 342 mounted thereon. The first pair of rollers 338, 340 is
positioned proximate to the first conveyor system 296 such mat the first film 342 is
suspended above the first plurality of porous platens 294. A second pair of rollers
344, 346 having a second film 348 mounted thereon is positioned proximate to the
second conveyor system 298 such that the second film 348 is also suspended above
the first plurality of porous platens 294
The vacuum forming apparatus 292 also includes a first registering device 350
positioned proximate to the first conveyor system 296 for properly positioning the
first film 342 relative to a core 10 that is positioned within the recess 310 of the
porous platen 294. A second registering device 352 is positioned proximate to the
second conveyor system 298 for properly positioning the second film 348 relative to a
partially enrobed core 10 that is positioned within the recess 310 of another of the
porous platens 294.
The vacuum forming apparatus 292 also includes a first ring press 354 and a
first film cutter 356 that are positioned proximate to the first conveyor system 296 and
move in a reciprocating fashion. Additionally, a second ring press 358 and a second
film cutter 360 are positioned proximate to the second conveyor system 298. The first
and second ring presses 354,358 each have an open configuration, such as an O-
shape or an oval shape, as viewed from above, such that there is formed a passageway
362,364, respectively, therethrough. Each of the ring presses 354,358 also has a
contacting edge 366,368, respectively, configured to contact the first and second
films 342, 348, respectively, without damaging them. Each of the ring presses 354,
358 is sized and shaped such that the contacting edges 366, 368 circumscribe a core
10 therein.
The first and second film cutters 356,360 each have a recess 370,372,
respectively, that is sized and shaped to receive therein a portion of a partially
enrobed core 10 which already has a film coating applied thereto. The first film cutter
356 is oriented to face the porous platen 294 positioned thereunder, while the second
film cutter 360 is oriented to face the porous platen 304 positioned thereunder. The
first and second film cutters 356, 360 also move reciprocatingly.
The first film 342 is mounted onto a first pair of rollers 338, 340 and stretched
therebetween, such that the first film 342 is positioned between the first conveyor
system 296 and the first plurality of porous platens 294 on one side, and the first ring
press 354 and the first film cutter 356 on the other side. Similarly, the second film
348 is mounted onto a second pair of rollers 344,346 and stretched therebetween,
such that the second film 348 is positioned between the second conveyor system 298
and the first plurality porous platens 294 on one side, and the second ring press 360
and the second film cutter 362 on the other side.
Initially, the first, second and third conveyor systems 296,298, 306 are set
into motion, thereby moving the porous platens 294,304 in the directions indicated by
the arrows BE, FF, GG, respectively, in Figure 31 of the [MCP 301]_________
application. The first conveyor system 296 moves one of the porous platens 294 to a
position that is immediately prior to the first station 378. A core 10 is placed into the
recess 310 of this porous platen 294 and held firmly in the recess 310 by the
aforementioned vacuum, which is continuously applied to the platen 294 and all
others on the conveyor 298, by a first vacuum source 300.
Platen 294 is next moved by the first conveyor system 296 to the first station
378. Movement of the platen 294 ceases temporarily when the first registering device
350 confirms that the core 10 is properly positioned. While the platen 294 is
momentarily stationary, hot air is blown through the first ring press 354, thereby
The platen 304 is then moved toward the partially enrobed core 10 until the partially
enrobed core 10 is held within the recesses 310, 312 of both of the platens 294, 304
(as shown in Figures 31 and 40 of the [MCP 301]_________- application). The
vacuum being applied to the porous platen 294 is discontinued and the platens 294,
304 are rotated with the partially enrobed core 10 therebetween, whereupon the platen
294 holding the core 10 is inverted, and the platen 304 is moved into a right-side-up
position. The now inverted platen 294 is now moved away from the right-side-up
platen 304 and becomes one of the platens 304 moving along the path shown by the
arrow GG in Figure 31 of the [MCP 301]_________— application. The right-side-up
platen 304 is next moved onto the second conveyor system 298 and becomes one of
the platens 294 moving along the path shown by the arrows EE, FF in Figure 31 of the
[MCP 301]________- application. Next, a vacuum is applied to partially enrobed
core 10, thereby holding the partially enrobed core 10 within the recess 310 of the
platen 294, which is now moving on the second conveyor system 298, such that the
uncovered portion of the partially enrobed core 10 is exposed.
Platen 294 and partially enrobed core 10 are moved by the second conveyor
system 298 to the fifth station 386 of the vacuum forming apparatus 292. Movement
of the platen 294 ceases temporarily when the second registering device 352 confirms
that the partially enrobed core 10 is properly positioned relative to the second film
248. While the platen 294 is momentarily stationary, hot air is blown through the
second ring press 358 to soften the second film 348 to a formable state. The second
ring press 358 is then moved such that the contacting edge 368 of the second ring
press 358 contacts and presses the second film 348 onto the working surface 314 of
the platen 294 and into contact with the uncovered portion of the partially enrobed
core 10.
The heated second film 248 is then pulled onto the core 10 by a vacuum
applied by the second vacuum source 302, thereby conforming the second film 248 to
the shape of the uncovered portion of the core 10. Thereafter, the second ring press
358 is retracted and the platen 294, having the enrobed core 10 held in its recess 310
by the vacuum, is now moved to the sixth station 388 and temporarily stopped there.
It is noted that, as shown in Figure 42 of the [MCP 301]__________application, the
softening the first film 342 to a formable state. The first ring press 354 is then moved,
such that the contacting edge 366 of the first ring press 354 presses the first film 342
onto the working surface 314 of the platen 294 and into contact with the top half of
the core 10.
The heated first film 342 is simultaneously pulled onto the core 10 and thereby
made to conform to the shape of the top half of the core 10 by the aforementioned
vacuum. Thereafter, the first ring press 354 is retracted and platen 294 is moved to
the second station 380, where it is temporarily stopped. While the platen 294 and the
core 10 are temporarily stationary, cold air is blown onto the first film 342 and core
10, thereby cooling and molding the first film 342 into conformity with the top half of
the core 10.
Referring to Figures 36-44 of the [MCP 301]_________application, after
sufficient time has passed to cool and mold the first film 342 onto the core 10, the
platen 294 and partially enrobed core 10 are moved a predetermined distance by the
first conveyor system 296 to the third station 382 of the vacuum forming apparatus
292 and temporarily halted there such that the partially enrobed core 10 is aligned
with the recess 370 and the cutting edge 374 of the first film cutter 356. The first film
cutter 356 is moved until the partially enrobed core 10 is received snugly within the
recess 370 and the tapered cutting edge 374 contacts and cuts through the first film
342 closely around the perimeter of the partially enrobed core 10. The first film cutter
356 is then moved away from the platen 294.
The platen 294 and partially enrobed core 10 are next moved to the fourth, or
rotating, station 384 of the vacuum forming apparatus 292 and, again, temporarily
stopped, whereupon the partially enrobed core 10 is transferred to one of the platens
304, as follows. The third conveyor system 306 moves one of the platens 304 into
position at the rotating station 384, such mat it is inverted relative to the platen 294
carrying the partially enrobed core 10 thereon. After the platen 294 is moved a
predetermined distance, such that the partially enrobed core 10 is aligned with the
recess 312 of the inverted platen 304, the first conveyor system 296 holds the platen
294 and partially enrobed core 10 temporarily stationary at the rotating station 384.
second film 348 partially overlaps the cut edge of the first film 342 that has already
been applied to the core 10. While the platen 294 and the core 10 are temporarily
stationary, cold air is now blown onto the second film 248 and core 10, thereby
cooling and molding the second film 348 into conformity with the core 10.
After sufficient time has passed to cool and mold the second film 348 onto the
core 10, the platen 294 and the enrobed core 10 are moved a predetermined distance
by the second conveyor system 298 to the seventh station 390 of the vacuum forming
apparatus 292 and temporarily halted there such that the enrobed core 10 is aligned
with the recess 372 and the cutting edge 376 of the second film cutter 360. The
second film cutter 360 is moved until the enrobed core 10 is received snugly within
the recess 372 and the cutting edge 376 contacts and cuts through the second film 248
closely around the perimeter of the enrobed core 10. The second film cutter 360 is
men moved away from the platen 294.
The platen 294 and fully enrobed core 10 are moved by the second conveyer
system 298 away from the seventh station 390. After the platen 294 and enrobed core
10 are past the seventh station 390, the vacuum being applied to the platen 294 is
ceased, thereby releasing the enrobed product 404 from the recess 310.
Alternatively, platens having recesses that are each circumscribed by a raised
cutting ridge capable of cleanly cutting the first and second films 342,348 may be
used. Alternatively, instead of first placing the caplet 10 into the recess 310 of the
first platen 294, the first film 342 could be laid across a first platen and then warm air
could be blown o&to the first film 342 to soften it to a formable state. Then, a vacuum
could be applied through the platen to pull the first film 342 into the recess and
conform it thereto. Thereafter, the core 10 could be placed into the recess 310 and
cool air blown onto the platen 294, first film 342 and core, to mold the first film 342
into conformity with the core 10. The second film 348 would then be placed onto the
platen, on top of the core 10, and warm air blown onto the second film 348 to soften it
to a formable state. Another platen would then be moved into contact with the second
film 348, pressing the second film 348 against the core 10 and the first platen 294,
thereby, conforming the second film 348 to the contour of the core 10. Cool air
determined by a Ubbelohde viscometer. Similarly, METHOCEL E6 , which is
another grade of HPMC-2910 suitable for use in the present invention, has a viscosity
of about 5 to 7 cps (5 to 7 millipascal-seconds) at 20°C in a 2% aqueous solution as
determined by a Ubbelohde viscometer. METHOCEL El5, which is another grade of
HPMC-2910 suitable for use in the present invention, has a viscosity of about 15000
cps (15 millipascal-seconds) at 20°C in a 2% aqueous solution as determined by a
Ubbelohde viscometer. As used herein, "degree of substitution" meand the average
number of substituent groups attached to a anhydroglucose ring, and "hydroxypropyl
molar substitution" meand the number of moles of hydroxypropyl per mole
anhydroglucose.
One suitable polyvinyl alcohol and polyethylene glycol co-polymer is
commercially available from BASF Corporation under the tradename KOLLICOAT
IR.
As used herein, "modified starches" include starches that have been modified
by crosslinking, chemically modified for improved stability or optimized
performance, or physically modified for improved solubility properties or optimized
performance. Examples of chemically-modified starches are well known in the art
and typically include those starches that have been chemically treated to cause
replacement of some of its hydroxyl groups with either ester or ether groups.
Crosslinking, as used herein, may occur in modified starches when two hydroxyl
groups on neighboring starch molecules are chemically linked. As used herein, "pre-
gelatinized starches" or "instantized starches" refers to modified starches that have
been pre-wetted, then dried to enhance their cold-water solubility. Suitable modified
starches are commercially available from several suppliers such as, for example, A.E.
Staley Manufacturing Company, and National Starch & Chemical Company. One
suitable film forming modified starch includes the pre-gelatinized waxy maize
derivative starches that are commercially available from National Starch & Chemical
Company under the tradenames PURITY GUM and F1LMSET, and derivatives,
copolymers, and mixtures thereof. Such waxy maize starches typically contain, based
upon the total weight of the starch, from about 0 percent to about 18 percent of
amylose and from about 100% to about 88% of amylopectin.
would then be blown onto the second film 348, thereby molding the second film 348
onto the caplet 10. Lastly, the raised cutting edges of the recesses may cut through
both of the first and second films 342,348, thereby releasing enrobed products.
It is noted that the hot and cold air temperature ranges, as well as the vacuum
pressure ranges, are within the knowledge of those skilled in the art.
In embodiments in which the shell is applied to the core by spraying, dipping,
enrobing, or molding, the shell is preferably applied to the core in the form of a
flowable material. The flowable material may comprise a dissolved, dispersed, or
molten component, and optionally a solvent or fluid carrier component that may
optionally be removed during processing, for example by drying. Regardless of the
method by which it is applied, the finished shell, and accordingly the flowable
material for making the shell, preferably comprises a film former. Optionally, the
shell or readily soluble shell portion of the present invention may further comprise
one or more thickeners, and various adjuvants and/or excipients as known in the art.
Any film former known in the art is suitable for use in the flowable material.
Examples of suitable film formers include, but are not limited to, film-forming water
soluble polymers, film-forming proteins, film-forming water insoluble polymers, and
film-forming pH-dependent polymers. In one embodiment, the film former may be
selected from cellulose acetate, ammonio methacrylate copolymer type B, shellac,
hydroxypropylmethylcellulose, and polyethylene oxide, and combinations thereof.
Suitable film-forming water soluble polymers include water soluble vinyl
polymers such as polyvinylalcohol (PVA); water soluble polycarbohydrates such as
hydroxypropyl starch, hydroxyethyl starch, pullulan, methylethyl starch,
carboxymethyl starch, pre-gelatinized starches, and film-forming modified starches;
water swellable cellulose derivatives such as hydroxypropyl cellulose (HDPC),
hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC),
hydroxyethyhnethylcellulose (HEMC), hydroxybutylmethylcellulose (HBMC),
hydroxyethylethylcellulose (HEEC), and hydroxyethylhydroxypropylmemyl cellulose
(HEMPMC); water soluble copolymers such as methacrylic acid and methacrylate
ester copolymers, polyvinyl alcohol and polyethylene glycol copolymers,
polyethylene oxide and polyvinylpyrrolidone copolymers; and derivatives and
combinations thereof.
Suitable film-forming proteins may be natural or chemically modified, and
include gelatin, whey protein, myofibrillar proteins, coaggulatable proteins such as
albumin, casein, casemates and casein isolates, soy protein and soy protein isolates,
zein; and polymers, derivatives and mixtures thereof.
Suitable film-forming water insoluble polymers, include for example
ethylcellulose, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose
acetate and its derivatives, acrylates, methacrylates, acrylic acid copolymers; and the
like and derivatives, copolymers, and combinations thereof.
Suitable film-forming pH-dependent polymers include enteric cellulose
derivatives, such as for example hydroxypropyl methylcellulose phthalate,
hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate; natural
resins, such as shellac and zein; enteric acetate derivatives such as for example
polyvinylacetate phthalate, cellulose acetate phthalate, acetaldehyde dimethylcellulose
acetate; and enteric acrylate derivatives such as for example polymethacrylate-based
polymers such as poly(methacrylic acid, methyl methacrylate) 1:2, which is
commercially available from Rohm Phanna GmbH under the tradename, EUDRAGIT
S, and poly(methacrylic acid, methyl methacrylate) 1:1, which is commercially
available from Rohm Pharma GmbH under the tradename, EUDRAGIT L, and the
like, and derivatives, salts, copolymers, and combinations thereof.
One suitable hydroxypropylmethylcellulose compound for use as a
thermoplastic film-forming water soluble polymer is "HPMC 2910", which is a
cellulose ether having a degree of substitution of about 1.9 and a hydroxypropyl molar
substitution of 0.23, and containing, based upon the total weight of the compound,
from about 29% to about 30% methoxyl groups and from about 7% to about 12%
hydroxylpropyl groups. HPMC 2910 is commercially available from the Dow
Chemical Company under the tradename METHOCEL E. METHOCEL E5, which is
one grade of HPMC-2910 suitable for use in the present invention, has a viscosity of
about 4 to 6 cps (4 to 6 milh'pascal-seconds) at 20°C in a 2% aqueous solution as
sorbose along with their hydrogenated analogs: e.g., glucitol (sorbitol), and mannitol
are preferred. Of the oligosaccharides, the 1,2-disaccharides sucrose and trehalose,
the 1,4-disaccharides maltose, lactose, and cellobiose, and the 1,6-disaccharides
gentiobiose and melibiose, as well as the trisaccharide raffinose are preferred along
with the isomerized form of sucrose known as isomaltulose and its hydrogenated
analog isomalt. Other hydrogenated forms of reducing disaccharides (such as maltose
and lactose), for example, maltitol and lactitol are also preferred. Additionally, the
hydrogenated forms of the aldopentoses: e.g., D and L ribose, arabinose, xylose, and
lyxose and the hydrogenated forms of the aldotetroses: e.g., D and L erythrose and
threose are preferred and are exemplified by xylitol and erythritol, respectively.
In one embodiment of the invention, the flowable material comprises gelatin
as a gelling polymer. Gelatin is a natural, thermogelling polymer. It is a tasteless and
colorless mixture of derived proteins of the albuminous class which is ordinarily
soluble in warm water. Two types of gelatin - Type A and Type B - are commonly
used. Type A gelatin is a derivative of acid-treated raw materials. Type B gelatin is a
derivative of alkali-treated raw materials. The moisture content of gelatin, as well as
its Bloom strength, composition and original gelatin processing conditions, determine
its transition temperature between liquid and solid. Bloom is a standard measure of
the strength of a gelatin gel, and is roughly correlated with molecular weight. Bloom
is defined as the weight in grams required to move a half-inch diameter plastic
plunger 4 mm into a 6.67% gelatin gel that has been held at 10°C for 17 hours. In a
preferred embodiment, the flowable material is an aqueous solution comprising 20%
275 Bloom pork skin gelatin, 20% 250 Bloom Bone Gelatin, and approximately 60%
water.
Suitable xanthan gums include those available from C.P. Kelco Company
under the tradenames KELTROL 1000, XANTROL 180, or K9B310.
Suitable clays include smectites such as bentonite, kaolin, and laponite;
magnesium trisilicate, magnesium aluminum silicate, and the like, and derivatives and
mixtures thereof.
Other suitable film forming modified starches include the hydroxypropylated
starches, in which some of the hydroxyl groups of the starch have been etherified with
hydroxypropyl groups, usually via treatment with propylene oxide. One example of a
suitable hydroxypropyl starch that possesses film-forming properties is available from
Grain Processing Company under the tradename, PURE-COTE B790.
Suitable tapioca dextrins for use as film formers include those available from
National Starch & Chemical Company under the tradenames CRYSTAL GUM or K-
4484, and derivatives thereof such as modified food starch derived from tapioca,
which is available from National Starch and Chemical under the tradename PURITY
GUM 40, and copolymers and mixtures thereof.
Any thickener known in the art is suitable for use in the flowable material of
the present invention. Examples of such thickeners include but are not limited to
hydrocolloids (also referred to herein as gelling polymers), clays, gelling starches, and
crystallizable carbohydrates, and derivatives, copolymers and mixtures thereof.
Examples of suitable hydrocolloids (also referred to herein as gelling
polymers) such as alginates, agar, guar gum, locust bean, carrageenan, tara, gum
arabic, tragacanth, pectin, xanthan, gellan, maltodextrin, galactomannan, pusstulan,
laminarin, scleroglucan, gum arabic, inulin, pectin, whelan, rhamsan, zooglan,
methylan, chitin, cyclodextrin, chitosan. Examples of suitable clays include smectites
such as bentonite, kaolin, and laponite; magnesium trisilicate, magnesium aluminum
silicate, and the like, and derivatives and mixtures thereof. Examples of suitable
gelling starches include acid hydrolyzed starches, and derivatives and mixtures
thereof. Additional suitable thickening hydrocolloids include low-moisture polymer
solutions such as mixtures of gelatin and other hydrocolloids at water contents up to
about 30%, such as for example those used to make "gummi" confection forms.
Additional suitable thickeners include crystallizable carbohydrates, and the
like, and derivatives and combinations thereof. Suitable crystallizable carbohydrates
include the monosaccharides and the oligosaccharides. Of the monosaccharides, the
aldohexoses e.g., the D and L isomers of allose, altrose, glucose, mannose, gulose,
idose, galactose, talose, and the ketohexoses e.g., the D and L isomers of fructose and
"Acid-hydrolyzed starch," as used herein, is one type of modified starch that
results from treating a starch suspension with dilute acid at a temperature below the
gelatinization point of the starch. During the acid hydrolysis, the granular form of the
starch is maintained in the starch suspension, and the hydrolysis reaction is ended by
neutralization, filtration and drying once the desired degree of hydrolysis is reached.
As a result, the average molecular size of the starch polymers is reduced. Acid-
hydrolyzed starches (also known as "thin boiling starches") tend to have a much lower
hot viscosity than the same native starch as well as a strong tendency to gel when
cooled.
"Gelling starches," as used herein, include those starches that, when combined
with water and heated to a temperature sufficient to form a solution, thereafter form a
gel upon cooling to a temperature below the gelation point of the starch. Examples of
gelling starches include, but are not limited to, acid hydrolyzed starches such as that
available from Grain Processing Corporation under the tradename PURE-SET B950;
hydroxypropyl distarch phosphate such as that available from Grain Processing
Corporation under the tradename, PURE-GEL B990, and mixtures thereof.
Suitable low-melting hydrophobic materials include fats, fatty acid esters,
phospholipids, and waxes. Examples of suitable fats include hydrogenated vegetable
oils such as for example cocoa butter, hydrogenated palm kernel oil, hydrogenated
cottonseed oil, hydrogenated sunflower oil, and hydrogenated soybean oil; and free
fatty acids and their salts. Examples of suitable fatty acid esters include sucrose fatty
acid esters, mono, di, and triglycerides, glyceryl behenate, glyceryl palrnitostearate,
glyceryl monostearate, glyceryl tristearate, glyceryl trilaurylate, glyceryl myristate,
GlycoWax-932, lauroyl macrogol-32 glycerides, and stearoyl macrogol-32 glycerides.
Examples of suitable phospholipids include phosphotidyl choline, phosphotidyl
serene, phosphotidyl enositol, and phosphotidic acid. Examples of suitable waxes
include carnauba wax, spermaceti wax, beeswax, candelilla wax, shellac wax,
microcrystalline wax, and paraffin wax; fat-containing mixtures such as chocolate;
and the like.
Suitable non-crystallizable carbohydrates include non-crystallizable sugars
such as polydextrose, and starch hydrolysates, e.g. glucose syrup, com syrup, and
high fructose corn syrup; and non-crystallizable sugar-alcohols such as maltitol syrup.
Suitable solvents for optional use as components of the flowable material
include water; polar organic solvents such as methanol, ethanol, isopropanol, acetone,
and the like; and non-polar organic solvents such as methylene chloride, and the like;
and mixtures thereof.
The flowable material for making the shell by spraying, dipping, enrobing, or
molding may optionally comprise adjuvants or excipients, which may comprise up to
about 30% by weight of the flowable material. Examples of suitable adjuvants or
excipients include plasticizers, detackifiers, humectants, surfactants, anti-foaming
agents, colorants, flavorants, sweeteners, opacifiers, and the like. Suitable plasticizers
for making the core, the shell, or a portion thereof, by molding include, but not be
limited to polyethylene glycol; propylene glycol; glycerin; sorbitol; triethyl citrate;
tribuyl citrate; dibutyl sebecate; vegetable oils such as castor oil, rape oil, olive oil,
and sesame oil; surfactants such as polysorbates, sodium lauryl sulfates, and dioctyl-
sodium sulfosuccinates; mono acetate of glycerol; diacetate of glycerol; triacetate of
glycerol; natural gums; triacetin; acetyltributyl citrate; diethyloxalate; diethyhnalate;
diethyl fumarate; diethylmalonate; dioctylphthalate; dibutylsuccinate;
glyceroltributyrate; hydrogenated castor oil; fatty acids; substituted triglycerides and
glycerides; and the like and/or mixtures thereof. In one embodiment, the plasticizer is
triethyl citrate. In certain embodiments, the shell is substantially free of plasticizers,
i.e. contains less than about 1%, say less than about 0.01% of plasticizers.
The openings may be made in the shell in any manner. A variety of methods
of creating openings or holes in coatings are known in the pharmaceutical and other
arts, and any of these may be used. As will be appreciated by one skilled in the art,
different methods of making the openings may lend themselves to combination with
different methods of manufacturing the dosage form and/or applying the shell thereto.
The method of making the openings also depends on the nature and composition of
the shell, and the outer coating if present. The openings may be formed in the shell of
the present invention at any of several different steps in the process, depending partly
on the process used to apply the shell to the core. For embodiments in which the shell
is applied to the core by enrobing, the openings may be formed during formation of
the cast film, after formation of the cast film but prior to application of the film to the
core, during application of the film to the core, or after application of the film to the
core. For embodiments in which the shell is applied to the core by dipping, transfer,
spraying, or molding, the openings may be formed in the shell material during
application of the shell to the core, or after application of the shell to the core.
For example, ablative methods employing erosion, melting, or vaporization of
the shell by water jet erosion, sand blasting, grinding, arc vaporization, dielectric
breakdown, ion beam sputtering, ultrasonic abrasive machining, cavitating fluid jet, or
laser evaporation may be used to make the openings. Mechanical processes such as
punching, perforating, slitting, piercing, drilling, masking followed by dipping, or
vacuum removal may be used to make the openings. Chemical means, such as acid
reactions, base reactions, solvent washing, acid etching with masking, photo etching
with masking, anisotropic wet chemical etching, isotropic wet chemical etching,
hydrophobization whereby dots of a nonwetting material are printed for example on a
roller, or a burned mask effect may be used to make the openings. Methods involving
the application of heat, such as melting with a hot iron, laser machining, arc
evaporation, ultrasonic melting or cavitation, microwave heating, high energy
methods such as plasma methods, infrared selective polymer curing, or induction
heating with ferrous additives may be used to make the openings. Finally, additive
methods such as painting, dipping, solvent washing, enrobing of the core with a
woven material, strands or ribbons, spray coating with a masking material and
removing the masking material by solvent or hydrophobic incompatibility, spraying
through a masking sheet, using ribbons of material, or building up threads or webs or
mats in the shell may also be used to create openings.
In one embodiment of the invention, the shell is applied to the core by thermal
cycle molding, as described above, and the openings are formed via one or more
protrusions on the inside surface of at least one of the mold assemblies. Each
protrusion, which is adjusted for shape and size as desired, masks a small location on
an underlying core, leaving behind an opening in the shell at the site of the protrusion.
The mold assemblies may comprise a plurality of protrusions to form a plurality of
corresponding openings in the shell. The protrusions may be located on the inside
surface of only one mold assembly, say the upper mold assembly, or located within
only a portion, i.e., one quadrant of the inside surface of one mold assembly, as
desired. Or the protrusions may be arranged to form patterns, symbols, words, and
the like, in the shell.
In another embodiment of the invention, the shell is applied to the core by
enrobing, either using visually homogeneous films as described in U.S. Patent Nos.
5,146,730 and 5,459,983, or films having visually distinct portions as described in
commonly assigned, copending U.S. Application Serial Nos. [MCP 301 and MCP
316]_________________. In either case, the cast films used for the enrobing step
are perforated either before, during, or after the enrobing process.
In one embodiment, in which the shell is applied to the core by enrobing, the
openings may be formed during formation of the cast film by the mechanical method
of casting the openings into the film using a suitably shaped or textured casting
surface, e.g. chilled film forming roll (exterier surface 36 of casting drum 34 in the
[MCP 301]____________application). Suitable textures include surfaces with
protrusions tall enough that the poured film will not envelope the protrusions, thus
leaving openings in the cooled film. Figure 7 depicts such a forming roll 1010 having
a surface 1020 having a suitable texture that creates voids, slits, or open areas in the
film. The films arrive at the dye rolls 1040 already containing openings.
In a second embodiment, in which the shell is applied to the core via enrobing,
the openings may be mechanically pierced or punched in the cast film after it is
formed, and prior to its application to the core. For example, Figures 8 and 9 depict
perforating apparatuses 1030 located between the forming rolls 1010 and dye rolls
1040. The perforating apparatus pierces, or punches openings into the formed film.
In another such embodiment, utilizing the vacuum forming method of applying the
shell to the core via enrobing, the film is vaccuum formed on a vacuum forming plate
(i.e., a plurality of porous platens 294 as described in the [MCP 301]________
application) into the cavity shapes for depositing the cores into the recess, then the
openings are formed prior to inserting the cores. In one particular such embodiment,
the shaped film with recesses is removed from the forming plate (i.e., the plurality of
porous platens 294), and travels to a perforating apparatus. In another particular
embodiment, the shaped film with recesses remains in contact with the forming plate
(i.e., the plurality of porous platens 294), and openings are formed therein via suitable
ablative methods prior to insertion of the cores. One particularly suitable ablative
method for this application employs a laser to "burn" the openings into the formed
film in the desired shape, size and pattern.
Another particular embodiment wherein openings are formed in the shell prior
to its application to the core by enrobing is depicted in Figure 10. This method
employs a capsule shell (comprising gelatin, starch, cellulose ethers, or other suitable
materials as known in the art and described herein) to enrobe the core of the dosage
form. The capsule shell is formed in two portions 1210 by dipping steel pins into a
solution of shell material in fluid form as known in the art. The shell material is then
solidified on the steel pins. Before removal of the solidified capsule shells from the
forming pins, suitable means, such as for example a laser, is used to burn the openings
in the capsule shell in the desired size, shape, and pattern. The cores 1220 are then
enrobed with the capsule shells 1210 as known in the art, for example by shrink-
fitring capsule shell halves onto compressed tablets as disclosed in U.S. Patent Nos.
5,415,868,6,126,767,5,464,631,5,460,824,5,317,849, 5,511,361, 5,609,010,
5,795,588 and 6,080,426, and PCT Appln. No. WO 97/37629 to produce a dosage
form 1230 of the present invention.
In a third embodiment the openings may be formed in the shell during the
application of the shell to the core. In such embodiments, the shell may be applied to
the core by any suitable method, e.g. enrobing, dipping, transfer, spraying, or
molding.
For example, in one embodiment wherein the shell is applied by enrobing, the
surface of the rotary dies 1040 have a suitable texture that creates voids, slits, or open
areas in the shell by perforating, piercing, or punching as the core is being enrobed
with the cast film.
One example of a method of forming openings in the shell during application
of the shell to the core by a dipping process is depicted in Figure 11. In mis method,
the core is held during dipping by a holder 1310 equipped with one or more,
preferably a plurality of masking pins 1320 that hold the core, and mask the areas to
be left uncovered by shell. The shape, size and arrangement of the masking pins 1320
determine the shape, size, and pattern of the openings in the shell. Another example
of a method of forming openings in the shell during application of the shell to the core
by a dipping process is depicted in Figure 12. Here the core is dipped into a foamed
shell material 1420. The air bubbles in the foam will become openings 1430 in the
finished solidified shell. In a similar embodiment, the openings are coreated during
application of the shell by dipping the core into a suspension of solid wax non-pareils
in film-forming shell material. The non-pareils are deposited onto the core along with
the shell material. The shell material is then solidified. Next, heat is applied in order
to melt the wax non-pareils, leaving openings in the shell in the size and shape of the
wax non-pareils. In another embodiment, the core is dipped into a fluid material, e.g.
polymer which reacts and solidifies upon activation by ultraviolet radiation, light, or
heat. In this method, a highly specific or targeted energy source such as a laser is
used to selectively solidify the portion of shell intended to remain on the tablet. After
this treatment, the remaining fluid either drains off or is washed off. In a similar
embodiment, the core surface may be coated with a powder, after which a laser can be
used to selectively melt portions of the powder, leaving unmelted powder where
openings are desired. The remaining material remains a powder and is shaken off.
One example of a preferred method of forming openings in the shell during
application of the shell to the core by a transfer method similar to printing is depicted
in Figure 13. A transfer plate 1510 surface has an engraved image with peaks and
valleys. The shell material is applied in fluid form to the surface of the transfer plate
1510, and selectively fills in the valleys but does not cover the peaks. A "print pad"
applicator 1520 picks up the shell material in the pattern of the image from the
transfer plate 1510 and deposits, or transfers, the shell material in the desired pattern
onto the surface of the core. Transfer plates offer the advantage of allowing indirect
application of the pattern to the dosage form. Another suitable method of painting the
shell material selectively onto the core is by powder coating, e.g. electrostatic
depostion as disclosed in PCT Appln. No. WO 01/57144. Another suitable method of
painting the shell material selectively onto the core is via ink jet printing as disclosed
in.
In a fourth embodiment, the openings may be formed in the shell after the
shell is applied to the core. One such embodiment is depicted in Figure 14. Here, the
core 1610 has protrusions 1620, the shell 1630 is applied to surround the entire core,
then the protrusions are ground off, e.g. by a pair of rotating grinding wheels 1640 to
expose uncoated core (i.e. create openings 1650). in yet another example, the shell is
applied to the core as multiple layers of a film, e.g. by enrobing. Areas of the film are
then selectively burned off with a laser to create openings in the shell surface in the
desired pattern and having any desired depth. In another such embodiment, a
scintering process is used to deposit the shell. Powdered shell material is applied to
the core surface, then heat is applied to partially, but not completely, fuse the powder
particles, creating a porous shell surface. Other preferred methods for forming
openings in the shell after its application to the core employ mechanical methods such
as punching, piercing, drilling, hot knive, melting. One such mechanical method is
depicted in Figure 15. Figure 15 A depicts the use of hot pins or knives to melt and/or
pierce the openings into the shell. Figure 15B depicts the drilling of openings in the
shell. The melting or piercing tips depicted in Figure 15 may form the surface (or
"business end") of either a punch mechanism, or a roller mechanism. Another
suitable mechanical method includes punching the openings into the formed shell as
depicted in Figure 16. In this particular embodiment, the punched-out shell material
remains in the cavity created by the punch, however a portion of the core surface
becomes exposed as part of the interior of the cavity. Alternate methods for forming
openings in the shell after its application to the core include ablative methods such as
sand/grit blasting, grinding, arc vaporization, dielectric breakdown, ion beam
sputtering, ultrasonic abrasive machining, cavitating fluid jet, laser evaporation;
chemical methods such as selective application acid or base reaction, chemical photo
etching; thermal methods such as melting using hot pins, laser machining, arc
evaporation, ultrasonic melting or cavitation, microwave heating, and the like. These
methods can optionally be employed to selectively remove shell material after first
masking the area of shell intended to remain intact.
It will be appreciated that many additional methods, including but not Limited
to those in the broad categories of ablative, mechanical, chemical, thermal, or
additive, though not specifically exemplified herein, are suitable for forming the
openings in the shell of the present invention.
For example, after exiting the film casting apparatus but before being fed to
the enrobing apparatus, the film sheets may be subjected to a mechanical process such
as punching, perforating, slitting, piercing, or drilling to form one or more openings in
the film sheets. For instance, slits may be formed in the cast or extruded film by
ablative, mechanical, chemical, thermal, or additive methods.
The following non-limiting example further illustrates the invention.
Total 603.2
The active and excipients of Part I are weighed in the proportions provided
and added to a bowl of a fluid bed granulator such as an AEROMATIC brand
granulator. The granulating agent (Part II) is prepared by adding the purified water to
a processing tank with approximately 15 grams of water for each gram of starch NF.
The starch is mixed in slowly, and the mixture is heated until the temperature reaches
about 82 to 84° C. With the components of Part I in a heated fluidized state and an
inlet air temperature of 75 to 85° C, the granulating agent is sprayed onto the
powders. After all the granulating agent has been sprayed, the granulated powders are
dried to a moisture content of about 1.4 to 1.9% as determined by loss on drying using
for example a COMPUTRAC brand analyzer. The dried granulation is then sieved,
for example, using a GLATT QUICK brand sieve stator No. 3, screen No. 1.5 mm,
1,000 RPM. The sieved and dried granulation is then blended with the powders of
Part HI using a suitable mixer such as a twin shell, ribbon or planetary mixer. The
finished blend is then loaded into the hopper of a rotary tableting machine and
compressed into tablets using round deep concave tooling having a diameter oil/16
inches. The average thickness of the resulting tablet cores is approximately 0.3 inches.
The average hardness of the resulting tablet cores is approximately 10 Kp. The
average tablet core weight is approximately 603.2 mg.
Part B: Preparation of Shell Material as Cast Film for Enrobing:
A first gelatin based cast film for enrobing the core of part A, having a
thickness in the range of approximately 0.02 inches, is prepared from the following
components:
Gelatin (150 Bloom) 45%
Glycerin 6%
Sorbitol 2%
Water 45%
Colorants 2%
The colorants are mixed with the water to form a homogenous soluiton. The
dry gelatin granules are added to the colorant solution, and mixed for about 1 minute
to completely wet the gelatin granules. The gelatin slurry is placed in a water bath
and heated to 55°C to melt and dissolve the gelatin. The glycerin and sorbitol are
then mixed in. The final solution is held at 55°C for approximately 10 hours to
deaerate. The solution is then mixed at low speed until uniform (about 5 to 15
minutes), and transferred to a jacketed feed tank equipped with a propeller-type
electric mixer. The gelatin solution is maintained at 55°C with continuous mixing
during its use for forming the cast film for making the first shell portion of the present
invention. The gelatin solution is then poured onto a casting drum (forming roll
1010), the surface of which is cooled to a temperature of approximately 25°C to form
a cast film.
A second gelatin based cast film having similar thickness, but a second color,
is prepared by the method described above.
The cooled first cast film is then fed between two rolls comprising a
perforating apparatus (1030), which punches openings into the formed film. The
openings are round, with a diameter of 750 microns, and are arranged in groups of 7,
with one central opening encircled by 6 peripheral openings. The groups of 7
openings are spaced in the film at intervals corresponding to the cavities in the dye
rolls 1040. The cooled second cast film is fed between two rolls with smooth
surfaces, thus remaining continuous with no openings therein.
Next, the perforated first film and the non-perforated second film are fed
between the dye rolls 1040, of an enrobing apparatus, together with the tablet cores of
part A. The first and second films are pressed in contact with the tablet core, and with
one another at an interface forming a seem around the belly band of the compressed
tablet core. The resulting dosage form has a first shell portion of a first color, having
openings therein, and a second shell portion of a second color, having substantially no
openings therein.
A dosage form containing at least one active ingredient, which
comprises a core and a shell surrounding at least a portion of the
core, wherein the core has a density of at least 0.9 g/cc, the shell
comprises one or more openings, the shell is readily soluble in
gastrointestinal fluids, and the dosage form provides for immediate
release of at least one active ingredient upon contact of the dosage
form with a liquid medium wherein the dosage form provides for
immediate release of at least one active ingredient contained in the
core which comprises a compressed tablet.

Documents:

748-KOLNP-2005-FORM-27.pdf

748-kolnp-2005-granted-abstract.pdf

748-kolnp-2005-granted-assignment.pdf

748-kolnp-2005-granted-claims.pdf

748-kolnp-2005-granted-correspondence.pdf

748-kolnp-2005-granted-description (complete).pdf

748-kolnp-2005-granted-drawings.pdf

748-kolnp-2005-granted-examination report.pdf

748-kolnp-2005-granted-form 1.pdf

748-kolnp-2005-granted-form 18.pdf

748-kolnp-2005-granted-form 2.pdf

748-kolnp-2005-granted-form 26.pdf

748-kolnp-2005-granted-form 3.pdf

748-kolnp-2005-granted-form 5.pdf

748-kolnp-2005-granted-reply to examination report.pdf

748-kolnp-2005-granted-specification.pdf


Patent Number 226786
Indian Patent Application Number 748/KOLNP/2005
PG Journal Number 52/2008
Publication Date 26-Dec-2008
Grant Date 24-Dec-2008
Date of Filing 28-Apr-2005
Name of Patentee McNEIL-PPC, INC.,
Applicant Address 199 GRANDVIEW ROAD, SKILLMAN, NJ
Inventors:
# Inventor's Name Inventor's Address
1 HARRY S. SOWDEN 209 WOODS ROAD, GLENSIDE, PA 19038
2 GERARD P. MCNALLY 177 COLDSTREAM DRIVE, BERWYN, PA 19312
PCT International Classification Number A61K 9/28, 9/20
PCT International Application Number PCT/US2003/008897
PCT International Filing date 2003-03-21
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 PCT/US02/31062 2002-09-28 U.S.A.
2 PCT/US02/31024 2002-09-28 U.S.A.
3 PCT/US02/31163 2002-09-28 U.S.A.
4 PCT/US02/31129 2002-09-28 U.S.A.
5 PCT/US02/3117 2002-09-28 U.S.A.