Title of Invention

A PROCESS FOR PREPARING BIOADHESIVE POLYMER COMPOSITIONS FOR TRANSMUCOSAL DRUG DELIVERY SYSTEMS WITH ENHANCED BIOADHESION

Abstract

1. A process for preparing bioadhesive polymer compositions for transmucosal drug delivery systems with enhanced bioadhesion comprising drug; a bioadhesive polymer gan and at least one nonpolymeric poly phenolic or poly hydroxy! excipient.such as herein described 2. The process as claimed in claim 1, wherein said non polymeric excipient increases the bioadhesive force of the bioadhesive polymer. 3. The process as claimed in claim 1, wherein said non polymeric excipient is a polyphenols compound. 4. The process as claimed in claim 3, wherein said non polymeric polyphenols excipient is a tannin. 5. The process as claimed in claim 4, wherein said tannin is selected from a group comprising of hydrolysable tannin or condensed tannin. 6. The process as claimed in claim 5, wherein said hydrolysable tannin is gaUitanrirn or elagitannin. 7. The process as claimed in claim 6, wherein said hydrolysable gallitannin is arjuna tannin. 8. The process as claimed in claim 5, wherein said tannin is tannic acid. 9. The process as claimed in claim 5, wherein said condensed tannin is catechu tannin. 10. The process as claimed in claim 1, wherein said non polymeric excipient is a polyhydroxy compound. 11. The process as claimed in claim 10, wherein said non polymeric polyhydroxy excipient is a carbohydrate. 12. The process as claimed in claim 11, wherein said carbohydrate is a monosaccharide or oligosaccharide. 13. The process as claimed in claim 12, wherein said oligosaccharide is lactose, mannitol. or sorbitol 14. The process as claimed in claim 13, wherein preferred said oligosaccharide is mannitol 15. The process as claimed in claims 1 to 14, wherein said non-polymeric polyphenols or polyhydroxy compound is at a concentration of 1-95%.

Full Text

THE PATENTS ACT, 1970 (39 of 1970) COMPLETE SPECIFICATION [See section 10; rule 13] 1. '-A PROCESS FOR PREPARING BIOADIIESIVE POLYMER COMPOSITIONS FOR TRANSMUCOSAL DRUG DELIVERY SYSTEMS WITH ENHANCED BIOADHESION" 2. (a) DEVARAJAN PADMA VENKITACHALAM (b) 12, Staff Quarters, UDCT Campus, Matunga, Mumbai 400 019. Maharashtra, India (c) Indian National The following specification (particularly) describes the nature of this invention and the manner in which it is to be performed: Technical Field This invention relates to process for preparing bioadhesive polymer compositions for transmucosal drug delivery systems with enhanced bioadhesion. This invention further relates to nonpolymeric polyphenols or polyhydroxy excipients for use in bioadhesive polymer compositions for enhanced adhesion. Background and Prior Art Modern pharmaceutical formulations may require a number of additives to carryout the complex activities ofa good drug delivery system. Thus, it may be necessary to solubilise a sparingly soluble drug, enhance the permeability of the drug across a biological membrane, have the dosage form adhere to particular site, inhibit the metabolising enzymes etc. Each of these functions is over and above the normal roles of formulation additives. Clearly, addition ofa separate agent for each of these functions would generate a very large dosage form and therefore it has become necessary to generate pharmaceutical excipients with multiple functions. Certain sites such as GIT and sublingual are very challenging in terms of developing retentive systems. The high mucus turnover rate and strong motility of GIT pose a major challenge in enhancement of residence time ofa dosage form. The sublingual site poses a problem because of large amounts of saliva that collect below the tongue, which may result in excessive hydration and formation of slippery mucilages with minimal or no bioadhesive properties. A two-phase, water absorbent bioadhesive composition is described in US Patent Application No. US 2003130427. The composition described contains both a hygroscopic phase and a hydrophilic phase. The composition claimed is useful as a bio-adhesive for affixing drug delivery systems. US Patent 6583225 describes a polymeric hydrogel of a polymeric anhydride or acid, crosslinked with a crosslinking agent such as polymeric ester or amide / imide, useful in bioadhesive products. A prolonged release bioadhesive mucosal therapeutic system containing at least one active principle, natural proteins and compression excipients comprising alkali metal alkyl sulphate and a monohydrate sugar is described in US Patent Application No. US 2003108603. US Patent 6562363 discloses bioadhesive compositions in a flexible, finite form for topical applications to skin or mucous membrane comprising a composition which results from admixture of at least one PVP polymer, at least one bioadhesive and optionally a suitable solvent. Methods and compositions for enhancing bioadhesive properties of polymers using organic excipients are described in US Patent Application US 2003077317 where incorporating a short chain polymer with one or more free carboxylic groups into the base polymer enhances the adhesive property. The base polymers in the form of microspheres have improved ability to adhere to mucosal membranes. US Patent Application US 2003065060 claims use of bioadhesive composition comprising a polyphenolic protein from byssus-forming mussels and a polymer comprising carbohydrate groups. Bioadhesive microsphere drug delivery systems having prolonged gastric retention time due to bioadhesion are described in Patent Application WO03051304. Polymers such as carbopol and chitosan act as multifunctional polymers with carbopol reported to inhibit the metabolic enzymes and chitosan acting as a permeation enhancer along with their bioadhesive properties. Among the bioadhesive polymers carbopol is reported to be one of the strongest bioadhesive polymer, however it has failed in increasing the transit time of a microparticulate system in GIT as revealed by a y-scintigraphic study. Increasing the concentration of a bioadhesive polymer should ideally increase the bioadhesion force of a polymer and therefore provide better retention. However, bioadhesion force is found optimum at a particular concentration beyond which the force decreases with increase in the polymer concentration. Thus, there is a need of a strong bioadhesive polymer or an excipient. which increases the bioadhesion force of existing polymers and performs other functions as well. Summary of the Invention This invention relates to bioadhesive polymer compositions for transmucosal drug delivery systems with enhanced bioadhesion. This invention further relates to nonpolymeric, polyphenoiic or polyhydroxy excipients for use in bioadhesive polymer compositions for enhanced bioadhesion. A process for making bioadhesive polymer compositions for transmucosal drug delivery systems with enhanced bioadhesion comprising drug; a bioadhesive polymer and at least one nonpolymeric poly phenolic or poly hydroxyl excipient, Detailed Description Bioadhesion is defined as a state in which two materials at least one of which is biological in nature are held together for an extended period of time by interfacial forces. If the adhesive attachment is to a mucus layer the phenomenon is referred to as mucoadhesion. The process of mucoadhesion involves two main components i.e. the polymers employed in drug delivery system and the mucus layer or mucosal epithelium. Bioadhesion is a reasonably complicated process, which involves physical interaction between two polymer networks (the mucus and the polymer) in an aqueous medium followed by establishment of stabilizing forces in terms of weak chemical bonds. Localisation of a drug delivery system using mucoadhesion can improve bioavailability of a drug, allows modification of tissue permeability, allows targeting of a drug and allows for inhibition of metabolizing enzymes in localized areas. The major component of these bioadhesive delivery systems is a bioadhesive polymer. Many commercially available polymers already known in the literature (e.g., Smart, J. D. et al, J.Pharm. Pharmacol., 1984, 36:295-99) as being bioadhesive can be used for this purpose. 4 Examples (without limitation) include: group of polymers consisting of cellulosics, starches, cross linked poly vinyl pyrrolidone, polymethacrylates, polyacrylates, xanthan gum, locust bean gum etc. Despite the good bioadhesive force of existing bioadhesive polymers, there are several sites wherein stronger bioadhesion is required, particularly at aites with high mucin turn over. Therefore there is a need for stronger bioadhesive polymers or a need for increasing the bioadhesive force of existing polymers. It was surprisingly found that polyphcnolic compounds as well as polyhydroxy compounds when used in combination with reported bioadhesive polymers increase the bioadhesion force of the reported polymers synergistically such that the formulation could be administered at sites of high mucus turnover. A process for making bioadhesive polymer compositions for transmucosal drug delivery systems with enhanced bioadhesion comprising mixinga drug; a bioadhesive polymer and at least one nonpolymeric poly phenolic or poly hydroxyl excipient. These polyphenols or polyhydroxy compounds act by virtue of their interaction with mucin and formation of secondary chemical bonds/interactions which increases the force require to separate the two surfaces, thus resulting in increased bioadhesion. A number of polyphenols compounds can be employed but of particular interest are a group of compounds known as tannins. The term tannin was first applied for the substances present in plant extract that were able to combine with protein of animal hides, prevent their putrefaction and convert them into leather. True tannins are the compounds, which give the Goldbeater's skin test positive. Tannins usually have molecular weight ranging from 1000-5000 and many of them are glycosides. Chemically tannins are moderately sized molecules of a substantial number of phenolic groups many of which are associated with O-dihydroxy and O-trihydroxy orientation within a phenyl ring. Tannins are classified into two classes, hydrolysable tannin and condensed tannin. Hydrolysable tannins are tannins, which may be hydrolysed by acids, or enzymes and they are further classified as galllitannins and ellagitannins. Examples of gallitannins are rhubarb, clove, galls, chestnut etc. and examples of ellagitannins include pomegranate. eucalyptus, oak bark etc. Condensed tannins (proanthocyanidines) include all tannins those are not hydrolysable for example cinnamon, tea, cinchona, acacia, catechu etc. Compounds which are of lower molecular weight and do not respond to Goldbeater's skin test even though they are polyphenols are known as pseudotannins which includes coffee tannins. Selection of nonpolymeric polyphenolic excipients and polyhydroxy excipient for combining with bioadhesive polymer needed to be based on the preferred structural features and other suitable properties of the target excipient. The preferred polyphenolic excipient selected by us for the preferred composition is a member of the tannin or tannic acid family. Non polymeric excipient studied is a polyphenolic compound, more specifically tannic acid or tannin. Preferably the selected tannins were arjuna tannin, tannic acid and catechu tannin. The non polymeric polyhydroxyl excipient studied is a carbohydrate. The carbohydrates studied are oligosachharides and monosachharides. The preferred carbohydrate is oligosachharides which are lactose, mannitol and sorbitol, more specifically mannitol. These non-polymeric, polyphenolic or polyhydroxy compounds themselves have no bioadhesive properties, but when combined with other bioadhesive polymers, they synergistically increase the bioadhesion force of these reported bioadhesive polymers. The concentration of these agents depend on a number of factors including: the desired bioadhesion force, the type of non-polymeric, polyphenolic or polyhydroxy excipient. and also on the type and concentration of the bioadhesive polymer employed. In general these agents can be used in the concentrations ranging from 1-95%, preferably in the range of 2-75% and most preferably in the range of 2.5-50%. The bioadhesive polymer that can be included in the formulation of the invention include polyacrylic polymers such as, carbomer and carbomer derivatives (Polycarbophil, Carbopol etc); cellulose derivatives such as hydroxypropylmethylcellulose (HPMC). hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC) and sodium 6 carboxymethylcellulose (NaCMC); natural polymers such as gelatin, sodium alginate, pectin; more generally, any physiologically acceptable polymer showing bioadhesivc characteristics may also be used. Also suitable as the bioadhesives are hydrophilic polysaccharide gums such as natural plant exudates, e.g., karaya gum, ghatti gum and the like, as well as seed gums, e.g., guar gum, locust bean gum, psyllium seed gum and the like. Cross-linked alginate gum gel of the type described in U.S. Patent No. 3,640,741 to Etes is also suitable for use as the mucoadhesive. Suitable commercial sources for representative bioadhesive polymers include: Carbopol acrylic copolymer - BF Goodrich Chemical Co., Cleveland, Ohio, USA. HPMC - Dow Chemical Co., Midland, Mich., USA. HEC (Natrosol) - Hercules Inc., Wilmington, Del., USA. HPC (Klucel) - Dow Chemical Co., Midland, Mich., USA. NaCMC - Hercules, Inc., Wilmington, Del., USA. Gelatin - Deamo Chemical Corp., Elmford, N.Y., USA. Sodium Alginate - Edward Mandell Co., Inc., Carmel, N.Y., USA. Pectin - BDH Chemicals Ltd., Poole Dorset, UK. Polycarbophil - BF Goodrich Chemical Co., Cleveland, Ohio, USA These polymers are employed at a concentration from 1-95%, preferably in the range of 2-85% and most preferably in the range of 5-75%. The active principle(s) are chosen in particular from an antihistamine, an anticholinergic, a mineral element, an allergen, a local or general surface anaesthetic, an antipyretic, a non-opiate analgesic, an opiate analgesic, an anticholinergic and non-anticholinergic antispasmodic, a non-steroidal anti-inflammatory such as indomethacin, diclofenac, ibuprofen, ketoprofen, naproxen, piroxicam, a steroidal anti-inflammatory such as betamethasone, prednisolone, a cyctotoxic agent, an antihormonal agent, an antianaemic. an antiemetic, an antiasthmatic, an antihypertensive and, of these, the beta-blocking agents such as propanolol, atenolol, metoprolol, angiotensin conversion enzyme inhibitors such as captopril, enalapril, angiotensin II antagonists, calcium antagonists such as nifedipine and diltiazem, central action antihypertensives, vasodilators, a hypolipemic, an oral antidiabetic, an anticoagulant, an antiplatelet drug, a calcium antagonist, a nitrate derivative used in the treatment of coronary insufficiency, a non-nitrate antianginal, a diuretic, a derivative of digitalin and allied products, an antiarrythmic, an antihypotensive and circulatory analeptic, a vasodilator, an antiischaemic, a vasculoprotector and a veinotonic, a hormone, an antiherpetic, an antiphotosensitiser, an antiulcer drug such as ranitidine, cimetidine, an antacid, a laxative, an antidiarrhoeal, an antifungal, a cholelitholytic, an interferon, an enzyme, an antispasmodic, an antibacterial, an antiseptic, an antiherpetic, a uturorelaxant, an oxytocic, an oestrogen, a progestogen, an oestroprogestogen, an active principle indicated in lactation such as bromocryptine, an active principle indicated in the treatment of sterility, an antigonadotropin, an anticoagulant, a thrombolytic, an antifibrinolytic, a vitamin, a haemostatic, a cyclosporin, an alkylating agent, an antibiotic, an antiviral, an antiparasitic, a vaccine, a diagnostic product, an active principle indicated in the treatment of obesity, an orexigenic, an active principle indicated in the treatment of corrections of metabolic anomalies, an active principle indicated in oral and enteral nutrition, an anticonvulsant, an antiparkinsonian drug, an antimy asthenic, an active principle indicated in the treatment of Alzheimer's disease, an antimigraine agent, a neuroleptic, an anxiolytic, a hypnotic, a sedative, an antidepressant, a normothymic. a psychostimulant, an active principle indicated in the treatment of dependency states in alcohol science, tobacco detoxification, opiate detoxification, an antiglaucoma agent, a mydriatic agent, a bronchodilator, an antiasthmatic, an antitussive, a bronchial expectorant, a (topical) counter-irritant, an active principle indicated in the treatment of osteopathies, an active principle indicated in the treatment of acute attacks of gout, an active principle indicated in the treatment of hypouricaemia, an active principle indicated in the treatment of algodystrophies, a muscle relaxant, an active principle indicated in the treatment of osteoarthritis, a corrector of hyposalivation, an active principle indicated in the treatment of urinary lithiasis, an active principle indicated in the treatment of renal insufficiency, an active principle indicated in the treatment of enuresis, an active principle indicated in the treatment of retrograde ejaculation, an active principle indicated in the treatment of impotence, and others. 8 The molecules contained in the composition according to the invention include contrast agents, radioelements, minerals and colouring agents, the list being non-limiting. The appropriate dosage for the pharmaceutical agents will often be approximately comparable to that of the pharmaceutical agent alone; dosages will be set by the prescribing medical professional considering many factors including age, weight, and condition of the patient, as well as the pharmacokinetics of the specific agent. Often the amount of agent required for effective treatment will be less than the amount required using the free pharmaceutical agent. Generally, an effective amount of pharmaceutical agent is that amount effective to reduce the symptoms of the disease sought to be treated, or to induce a pharmacological change relevant to treating the disease sought to be treated. The formulation can be in the form of various dosage forms such as a capsule, a tablet, a wafer, a chewable tablet, a buccal tablet, a sub-lingual tablet, a granule, a pellet, a bead. micro/nanoparticles, a pill, a sachet, a sprinkle, a film, a lozenge, a troche, an implant, a strip, a gel or a spray. These pharmaceutical compositions can be formulated for immediate release, pulsatile release, controlled release, extended release, delayed release, targeted release, or targeted delayed release. Also the compositions can be formulated for oral, nasal, ocular, urethral, buccal, transmucosal, vaginal, topical or rectal delivery. For development of these dosage forms this novel excipient can be combined with other excipients such as water soluble polymer, water insoluble polymers, hydrophobic materials, hydrophilic materials, waxes, disintegrants, superdisintegrants, diluents, binders, lubricants, absorption promoters, solubilising agents, aromatisers, flavour masking agents, sweeteners, colouring agents, plasticizers, antioxidants, stabilizers etc. Advantages of the invention: Use of the non-polymeric, polyphenols or polyhydroxy excipients in the formulation helps to 9 > Increased bioadhesive force of the polymer for sublingual as well as GIT administration. > Allows reduction in the amount of bioadhesive polymer employed for retentive systems. > Use lower amounts of polymers with sufficient bioadhesion force which are most suited for immediate release bioadhesive systems. > Carryout multiple functions such as penetration enhancement, inhibition of enzymes, taste masking etc., and > Allows reduction in the cost of the manufacturing. Example 1: Bioadhesive property of Tannic acid. Tannic acid was compressed into 8 mm tablets using standard excipients and conventional tableting techniques. The concentration of tannic acid was kept at 10% w/w and the tablets were evaluated for bioadhesive property using guinea pig ileum. Bioadhesion test was carried out using modified Peel Adhesion Tester (Lami Coat Equipments, Thane) Equipment consisted of two clamps designed to hold the test cells (Plate 3). For guinea pig ileum as substrate, the ileum was stuck with the help of an adhesive to the cells without cavity. The tablet was stuck to the surface of the upper cell with the help of an adhesive. Tablet surface was wetted with a 20 ul medium. The test cells were then placed in cell holders and the two surfaces were kept in contact for 2 min. at the force of 400 x 103 dynes. After 2 min the upper test cell holding the tablet was pulled at a speed of 50 mm/min and the detachment force was recorded. The bioadhesion force obtained for these tablets was less than 30 x 103 dynes. These results indicate that tannic acid at concentration of 10 %w/w is not a good bioadhesive. The possible reason for this poor bioadhesive nature of tannic acid may be the lack of polymeric nature because of its low molecular weight. Example 2: Synergism in bioadhesion force Tablets of various bioadhesive polymers such as sodium CMC, Hydroxypropyl cellulose E5, Hydroxypropyl cellulose EXF, and Sodium alginate were prepared in 1:1 ratio with tannic acid at the concentration of total 20 % (i.e. 10+10 %). A model drug ketorolac tromethamine (KT) at 10 % w/w concentration was also incorporated in the system containing Sodium alginate and tannic acid. The results indicate that for all polymers a synergistic effect was obtained (Fig. 1) which means that the bioadhesion force for the combination was greater than the sum of the individual contribution of polymer towards bioadhesion force. Bioadhesion force for tannic acid alone was 28.50 ± 10.64. Taking example of sodium alginate, bioadhesion force for sodium alginate was 120.88 ± 14.06 x 103 dynes at 10 % w/w concentration. When 1:1 tannic acid was added to sodium alginate the bioadhesion force was found to increase to 171.11 ± 18.90 x 103 dynes. A similar result was also obtained with other bioadhesive polymers. A study was also carried out with incorporation of a drug ketorolac tromethamine in polymer combination. Incorporation of drug although resulted in a decrease in bioadhesion force for individual polymers, a synergistic effect was still observed. As evident from Fig. 2 arjuna tannin and catechu tannin also synergistic ally increased the bioadhesive force of Sodium alginate. These results suggest that the property of increasing the bioadhesion force of polymers resides with a family of compounds having similar structures and the properties. Description of Drawings: Fig 1 illustrates the results of bioadhesion force obtained for all polymers with a synergistic effect which means that bioadhesion force for the combination was greater than the sum of the individual bioadhesion force of polymer. Bioadhesion force for the non polymeric polyphenols excipients like tannin alone was shown by block with the lines inside (1). Column representing by number 2 shows the bioadhesion force for bioadheisve polymers like Carboxy methyl cellulose (CMC), Hydroxy propyl methyl cellulose (HPMC), Sodium alginate(SA), Hydroxy propyl cellulose (HPC), and column 3 is for non polymeric polyphenols excipients like tannin in combination with each of the bioadhesive polymers mentioned above in 1:1 ratio. X-axis (9) indicates the different combination or individual bioadhesive polymer and Y-axis (10) is for bioadhesion force in dynes. Numbers 4 shows group of three columns wherein first column is for bioadhesion force obtained for tannic acid, second column foT bioadhesion force of bioadhesive polymer, CMC and third for bioadhesion force of combination of bioadhesive polymer, CMC with tannic acid. Number 5 represents group of three columns wherein first column is for bioadhesion force obtained for tannic acid, second column for bioadhesive polymer, HPMC and third for combination of bioadhesive polymer, HPMC with tannic acid. Number 6 represents group of three columns wherein the first column is for bioadhesion force obtained for tannic acid, second column is for bioadhesive polymer, SA and third is for combination of bioadhesive polymer, SA with tannic acid. Number 7 represents group of columns wherein first column is for bioadhesion force obtained for tannic acid, second column is for bioadhesive polymer, SA in combination with a drug ketorolac tromethamine and third is for combination of bioadhesive polymer, SA in combination with tannic acid and drug ketorolac tromethamine. Number 8 represents group of three columns wherein first column is for bioadhesion force obtained for tannic acid , second column for bioadhesive polymer , HPC and third for combination of tannic acid with HPC. Fig 2 shows the similar synergistic effect in bioadhesion force of sodium alginate with arjuna tannin and catechu tannins. These results clearly indicate that the property of increasing the bioadhesion force of polymers resides with a family of compounds having similar structure and properties. X- axis (11) indicates individually tannin or sodium alginate or combination of both. Y-axis (12) indicates the bioadhesion force in dynes. Number 16 represents group of three columns wherein first column (13) represents bioadhesion force of Arjuna Taanin, second column (14) for bioadhesion force of Sodium alginate and third column (15) for bioadhesion force of combination of Arjuna Tannin and sodium alginate. Number 17 represents group of three columns wherein first column (13) represents bioadhesion force of Catechu Tannin, second column (14) represents I Claim 1. A process for preparing bioadhesive polymer compositions for transmucosal drug delivery systems with enhanced bioadhesion comprising drug; a bioadhesive polymer gan and at least one nonpolymeric poly phenolic or poly hydroxy! excipient.such as herein described 2. The process as claimed in claim 1, wherein said non polymeric excipient increases the bioadhesive force of the bioadhesive polymer. 3. The process as claimed in claim 1, wherein said non polymeric excipient is a polyphenols compound. 4. The process as claimed in claim 3, wherein said non polymeric polyphenols excipient is a tannin. 5. The process as claimed in claim 4, wherein said tannin is selected from a group comprising of hydrolysable tannin or condensed tannin. 6. The process as claimed in claim 5, wherein said hydrolysable tannin is gaUitanrirn or elagitannin. 7. The process as claimed in claim 6, wherein said hydrolysable gallitannin is arjuna tannin. 8. The process as claimed in claim 5, wherein said tannin is tannic acid. 9. The process as claimed in claim 5, wherein said condensed tannin is catechu tannin. 10. The process as claimed in claim 1, wherein said non polymeric excipient is a polyhydroxy compound. 11. The process as claimed in claim 10, wherein said non polymeric polyhydroxy excipient is a carbohydrate. 12. The process as claimed in claim 11, wherein said carbohydrate is a monosaccharide or oligosaccharide. 13. The process as claimed in claim 12, wherein said oligosaccharide is lactose, mannitol. or sorbitol 14. The process as claimed in claim 13, wherein preferred said oligosaccharide is mannitol 15. The process as claimed in claims 1 to 14, wherein said non-polymeric polyphenols or polyhydroxy compound is at a concentration of 1-95%. 16. The process as claimed in claim 15, wherein said non-polymeric polyphenols or polyhydroxy compound is preferably at a concentration of 2-75%. 17. The process as claimed in claim 16, wherein said non-polymeric polyphenols or polyhydroxy compound is used most preferably at a concentration of 2.5-50%. 18. The process as claimed in claim 1, wherein said drug is selected from the therapeutic categories consisting of (3-blockers, antiarrhythmic agents, calcium antagonist, anti hypertensive agents, anti anginal agents, opiate analgesics, anti bacterial agents, anti malarials, sedatives, anti depressants, antiulcer drug, vasodilators, antiemetics, muscle relaxants, anti-fungal, expectorants, bronchodilators, anti allergies, analgesics, anti¬inflammatory, antibiotics, fungicides, chemotherapeutic agents, oral antiseptics. protein and peptides and anti migraine drugs. 19. The process as claimed claim 1, wherein said bioadhesive polymer is selected from a group consisting of cellulosics, alginates, starches, vinyl polymers, polymethacrylates, polyacrylates, xanthan gum, locust bean gum, etc. 20. The process as claimed in claim 19, wherein said bioadhesive polymer is a cellulosic polymer. 21. The process as claimed in claim 20, wherein said bioadhesive cellulosic polymer is sodium carboxy methyl cellulose. 22. The process as claimed in claim 19, wherein said bioadhesive polymer is sodium alginate. 23. The process as claimed in claims 1 and 19 to 22, wherein said bioadhesive polymer is at a concentration of 1-95%. 24. The process as claimed in claim 23, wherein said bioadhesive polymer is preferably at a concentration of 2-85%. 25. The process as claimed in claim 24, wherein said bioadhesive polymer is most preferably at a concentration of 5-75%. 26. The process as claimed in claims 1 to 25, wherein said mucosal drug delivery system comprises a capsule, a tablet, a wafer, a granule, a pellet, a bead, a pill, a sachet, a sprinkle, a film, a strip, a gel. a solution, a spray, microparticles, nanoparticles. suppository. 27. The process as claimed in claims 1 to 26. wherein said mucosal drug delivery system comprises additional excipients such as water soluble polymers, waxes, diluents, super disintegrants, and other pharmaceutical excepient necessary for the development of a dosage form in the form of a capsule, a tablet, a wafer, a granule, a pellet, a bead, a sachet, a sprinkle, a film, a strip, a gel, a solution, a spray, microparticles, nanoparticles, suppository. 28. The process as claimed in claims I to 27, wherein said mucosal drug delivery system is in the dosage form like immediate release dosage form, pulsatile release dosage form, controlled release dosage form, extended release dosage form, delayed release dosage form, targeted release dosage form, or targeted delayed release dosage form. Dr. Gopakumar G. Nair Agent for the Applicant Dated this the 20th day of Oct 2003

Documents:

1107-mum-2003-abstract(15-12-2003).doc

1107-mum-2003-abstract(27-1-2005).pdf

1107-mum-2003-cancelled pages(27-1-2005).pdf

1107-mum-2003-claims(granted)-(27-1-2005).doc

1107-mum-2003-claims(granted)-(27-1-2005).pdf

1107-mum-2003-claims.doc

1107-mum-2003-claims.pdf

1107-mum-2003-correspondence(27-1-2005).pdf

1107-mum-2003-correspondence(ipo)-(7-1-2005).pdf

1107-mum-2003-correspondence(ipo).pdf

1107-mum-2003-correspondence.pdf

1107-mum-2003-description(granted).doc

1107-mum-2003-description(granted).pdf

1107-mum-2003-drawing(27-1-2005).pdf

1107-mum-2003-drawing.pdf

1107-mum-2003-form 1(15-12-2003).pdf

1107-mum-2003-form 1(19-1-2005).pdf

1107-mum-2003-form 1(28-5-2004).pdf

1107-mum-2003-form 1-19-may-2005.pdf

1107-mum-2003-form 1-28-may-2004.pdf

1107-mum-2003-form 1.pdf

1107-MUM-2003-FORM 15(31-7-2012).pdf

1107-mum-2003-form 19(15-12-2003).pdf

1107-mum-2003-form 19.pdf

1107-mum-2003-form 2(granted)-(27-1-2005).doc

1107-mum-2003-form 2(granted)-(27-1-2005).pdf

1107-mum-2003-form 2(granted).doc

1107-mum-2003-form 2(granted).pdf

1107-mum-2003-form 2(title page).pdf

1107-mum-2003-form 26(29-8-2003).pdf

1107-mum-2003-form 3(20-10-2003).pdf

1107-mum-2003-form 3.pdf

1107-mum-2003-power of attorney.pdf

1107-mum-2003-search report.pdf

abstract1.jpg