Title of Invention

AN APPARATUS FOR HEATING METERED DOSE INHALERS

Abstract

An apparatus is claimed for heat stress testing of metered dose inhalers (10) to detect and reject non-conforming inhalers. The apparatus includes an electrical power supply (32) and one or more induction coils (24,26,28). The induction coil (24,26,28) is suitably sized and configured to directly heat each entire inhaler (10). A computer controlled gating assembly (22a, 22b, 22c) is included and contains first and second heat exchangers (40,42) employed to straddle a first metered dose inhaler (10') and a second metered dose inhaler (10") so that they are positioned proximate to these inhalers during the heating cycle. As a result of the proximate positioning, heating inefficiencies are reduced.

Full Text

AN APPARATUS FOR HEATING METERED DOSE INHALERS FIELD OF THE INVENTION The present invention generally relates to the field of medicament inhalation devices, specifically metered dose inhalers, and to heat stress testing of such inhalation devices to detect and reject nonconforming inhalers. BACKGROUND OF THE INVENTION In the art of manufacturing medicament aerosol inhalation devices, recent attention has been aimed at detecting and rejecting potential and actual nonconforming devices. For example, a small percentage of aerosol inhalation devices leak or will leak due to manufacturing defects, such as broken or torn gaskets, loss of proper sealing, defective valve, swollen gasket(s), etc. Such defects cause a loss of aerosol propellant, which adversely affects or otherwise alters the performance of the inhalation device. Recently, the Food and Drug Administration ("FDA") has become very concerned with leaking (or otherwise nonconforming or defective) aerosol inhalation devices, particularly MDI's. The performance of an MDI can be significantly altered when the propellant leaks, particularly where the propellant leaks in significantly amounts or at a significant rate. For example, a "gross leaker" may not deliver the medicament at all to the patient, MDI's that leak at more than an insignificant rate may under deliver the medicament. In other words, the medicament delivery from a leaking MDI does not conform to the dosing regimen set forth and approved by the FDA. In that case, the patient may not even realize that the insufficient medicament is being delivered to the lungs. As a result, the FDA has begun requiring manufacturers to stress test aerosol inhalation devices and subsequently weigh the stressed devices to detect actual and potential nonconforming devices. Leaking MDI's will weigh less than what they are supposed to weigh- Stressed MDI's that lose a predetermined amount of propellant are rejected as nonconforming. The FDA has set conforming standards. The FDA has also set a temperature standard of 55°C ±5C° for heat stress testing the MDI's. Many methods and apparatus are available for heating MDI's. The present invention involves using electromagnetic induction heating to heat the electro-conductive materials present in the MDI, such as primarily the aluminum canister, Electromagnetic induction is a method of generating heat within a metal part. Any electrical conductor can be heated by electromagnetic induction. As alternating current from the generator flows through the inductor, or work coil, a highly concentrated, rapidly alternating magnetic field is established within the coil. The magnetic field thus induces an electric potential in the part to be heated. The part represents a closed circuit. The induced voltage causes current to flow within the part. Eddy currents are typically established. The resistance of the part to the flow of the induced current causes heating. The pattern of heating obtained by induction is determined by a number of factors: the shape of the induction coil producing the magnetic field, the number of turns in the coil, the operating frequency, the alternating current power input, and the nature of the work pieces. The rate of heating obtained by the coils depends on the strength of the magnetic field to which the part is exposed. In the work piece, this becomes a function of the induced currents and the resistance to electrical flow. The depth of current penetration depends upon work piece permeability, resistivity, and the alternating current frequency. Since the first two factors vary comparatively little, the greatest variable is frequency. Depth of current penetration decreases as frequency increases. High frequency current is generally used when shallow heating is desired. Intermediate and low frequencies are used in applications requiring deeper heating. The induction coil and associated components and the processes thereof of the present invention are advantageous. The present invention advantageously heats and stress tests MDI's in a relatively short period of time (i.e., dwell time), which permits in-line processing at high throughput. The present invention also advantageously employs a few relatively simple processing and material handling equipment resulting in low investment, reduced maintenance, high efficiency, and reliability. The present invention relates to the heat exchangers straddling the first and last MDIs so that they are positioned proximate to the first and last MDIs during the heating cycle. The present invention is further advantageous in that only the electroconductive portions of the MDI are heated significantly reducing the heating of plastic components (e.g. gaskets and valve components) that are susceptible to being unnecessarily damaged by heat. Still further, the present invention advantageously heat stress tests 10 the MDI's without exposing the MDl's to steam or moisture (except any negligible moisture associated with the sealed heat exchangers) which can ingress into the MDI reducing product performance. US 3,229,513 discloses methods for detecting surface defects on solid articles by using a halogen containing liquid on the surface of the article, wherein an induction coil is employed to vaporize liquid from the surface of the article. However, US 3,229,513 does not teach employing first and second heat exchangers in conjunction with metered dose inhalers. Further, US 4,220,839 relates to an induction heating coil for the crucible free melting of crystalline material. In particular, the coil heats a polycrystalline feed stock rod to a single crystal rod (Fig.2). However, it does not teach employing first and second heat exchangers in conjunction with metered dose inhalers. Also, US 4,878,379 relates to rheometers containing shearing elements for subjecting an intervening sample of material to shear forces and more specifically rotational rheometers. However, it does not teach employing first and second heat exchangers in conjunction with metered dose inhalers. SUMMARY OF THE INVENTION One aspect of the invention is an apparatus for heating medicinal inhalation devices. The apparatus includes an electrical power supply and one or more induction coils. Preferably, the apparatus further includes a microprocessor for controlling the power supply in the range of 100-130 amps, preferably 110-115 amps, and more preferably about 113 amps, to heat the inhalation devices to a temperature in the range of 50-60°C, preferably around 55°C. By "about" or the like language as used herein, it is meant to include those values surrounding the recited value or range of values that achieve substantially the same desired ultimate result. The apparatus also preferably further includes a cooling system including a condenser and a pump, wherein a liquid coolant is pumped through the induction coil. Preferably, the power supply provides up to 20 kilowatts (kW) at a frequency in the range of 240-440 kHz. A vojtage of 140 volts may be applied to the induction coils. The electrical power supply may be operated in the range of 80-90% efficiency, preferably about 85%. The induction coil may be constructed from copper tubing and silver soldered joints. Preferably, the induction coil is a single, continuous coil in the shape of a loop having first and second bridges, one at each end of the loop, respectively. The bridges are suitably sized and configured to directly heat each entire inhalation device. In other words, the bridges of the induction coil may be 4 inches in height for heating metered dose inhalers ("MDI's") that are 2-3 inches in height. Examples of MDI's that may be stress tested by this invention include those disclosed in USPN's 8,170,717; 6,131.566; 6,5 43,2//; and 6,149,892, which are incorporated herein by reference. Another aspect of the invention is an apparatus including the electrical powers supply and induction coil(s) described herein above, a conveyor, and a gating assembly for indexing a predetermined number of medicinal inhalation devices along the conveyor between the bridges of the Induction coil. Preferably, the gating assembly further includes first and second heat exchangers suitably adapted and positioned to heat the first and last metered dose inhaler cycled and indexed within the induction coil. The heat exchanger may include an aluminum canister (similar to the canister used in the MDI's) adapted to be cooled by circulating cooling water. Preferably, the gating assembly is adapted and controlled to index 32 metered dose inhalers per heating cycle. The MDI's are indexed one sfug at a time where each slug may include 8 MDI's. Each heating cycle may include 4 slugs of 8 metered dose inhalers per slug. The heating cycle time may be in the range of 30-40 seconds. As such, the conveyor may have a line speed in the range of 100-140 metered dose inhalers per minute. An infrared thermometer may also be employed to measure the temperature of the metered dose inhalers. Preferably, the measured temperatures are fed to the microprocessor, whereby the microprocessor adjusts the power supply to heat the metered dose inhalers to the desired temperature, for example 55°C ± 5C°. A check weighing device is also preferably employed to check the weight of the heated metered dose inhalers. Any nonconforming and/or leaking (e.g., gross leakers) MDI's are detected and summarily rejected/discarded. Another aspect of the invention is a process or method of heat stress testing medicinal inhalation devices to detect and reject nonconforming or leaking devices. In general, the process includes providing one or more inhalation devices, and induction heating the one or more inhalation devices. Preferably, the inhalation devices are metered dose inhalers, whereby the metered dose inhalers are provided continuously (e.g., continuous runs) at a line speed in the range of 100-140 inhalers per minute. Preferably, the process also includes indexing the continuously provided metered dose inhalers. The metered dose inhalers may be indexed in slugs of 8 providing 32 metered dose inhalers per induction heating cycle. During the heating cycle, the metered dose inhalers are preferably heated to a temperature in the range of about 50-60°C, preferably about 55ºC. The temperature of the metered dose inhalers, the indexing, the induction heating, and other steps in the process may be computer process controlled by a microprocessor and other suitable electronic (e.g., sensors) and electromechanical equipment and instruments (e.g., pneumatic actuators). The process preferably also includes the steps of check weighing the heated metered dose inhalers, and rejecting any nonconforming or leaking metered dose inhalers. ACCOMPANYING DESCRIPTION OF THE/DRAWINGS Fig. 1 is a top view ot one aspect of the present invention. Fig. 2 is a side view of a portion of the gating assembly and heat exchanger of the present invention. • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Shown in Fig. 1 is a top view of various aspects of the invention. A plurality of medicament inhalation aerosol devices 10, such as MDI's, are conveyed along a conveyor 12. The MDI's 10 are loaded onto the conveyor 12 from a tray unloading station 14. From there, the MDI's 10 pass along the conveyor 12 past a backup cue sensor 16 to between rails 18. A can count sensor 20 keeps track of the number of MDI's 10 passing that point on the conveyor 12. A computer-controlled gating assembly 22a,22b,22c indexes a predetennined number of MDI's 10 (called a slug, e.g., 8 MDI's per slug) into a zone above a channel portion 24 of an induction coil and between the end bridge portions 26,28 of the induction coil. Preferably, the induction coil is a continuous loop, single tube, single turn, channel/radiused type induction coil fabricated from copper tubing and silver soldered joints, such as those available from Pillar Industries of Brookfield, Wl. The coil 24,26,28 is water cooled using a chiller (not shown), and is pressure rated for 100 psi. Preferably, ihe channel 24 is about 4 feel long and the coil has a 0.75 inch face width to accommodate various MDI 10 sizes and configurations. One of gating assembly levers 22c accumulates the MDi's 10 prior to entering the induction zone, and the other gating assembly levers 22a,22b are preferably pneumatically actuated during the induction heating cycle. "The MDl's 10 can be alternatively indexed using a feedscrew or starwhee) assembly. Preferably, 4 slugs of 8 MDl's 10 are indexed into the induction heating zone per heating cycle, thus having 32 MDl's heated per cycle. Preferably, the dwell time of the MDl's-10 in the heating induction cycle is around 9 seconds for 32 MDl's. A single slug of 8 MDl's may be indexed in 5 seconds. The heated MDl's 10 may be removed from the induction zone in around 3 seconds. Thus, line speeds of around 120 or greater MDl's per minute are preferably achieved. The gating assembly desirably allows the conveyor to run at a constant line speed. The number of MDl's in each heat induction cycle affects the heating efficiency. In general, coil efficiency is improved by increasing the number of MDl's. In general, MDl's heat faster in a static mode, so the 'indexing method is more effective than where the MDl's are moving. A safety enclosure 30 constructed from LEXAN© is also preferably provided. A controlled electrical power supply 32 having a control panel 34 supplies electrical power to the bus bar 36 which, in turn, supplies power to the induction coil 24,26,28. Preferably, the power supply 32 is a 20kW, 400kHz solid state RF generator, such as those available from Pillar Industries, MK-20, Model 7500. After completion of the heating cycle, the gating assembly 22a,22b releases the MDl's 10 conveying the MDl's 10 along the conveyor 12 to the accumulation table 38. A check weighing device (not shown) may be employed prior to or after the accumulation table 38 to detect and reject nonconforming (e.g., marginal sealing, defective valve, poor crimp, cut gasket, faulty component, etc.) or otherwise leaking (e.g., gross leaker) MDl's 10. Preferably, the power supply 32 has a built-in timer that can be set according to the time necessary to heat a predetermined number of MDl's to a desired temperature or temperature range. For example, it may take 4 second to induction heat 32 MDl's 10 to 54-60°C. The weight /nay be checked in-line or offiina. A suitable check-weighing device is available from Anritsu. An infrared thermometer 38msy bo used to measure the temperature of the MDI's 10 to ensure proper heating. Such measurements may be fed to the computer controlled power supply 32 to control heating. An irreversible temperature indicator may also be used by putting the test strip inside the MD110 and removing it after the heating cycle to determine the maximum temperature reached in the MDI. The infrared thermometer (Mode! OS91) and temperature test strips (Model U-08068-22) are available from Cole-Parmer Shown in Fig. 2 is a preferred embodiment of the outer canister heat exchangers 40,42 of the present invention. The heat exchangers 40,42 are fixedly or removably attached to the non-conductive, placement arm of the gating assembly 22a,22b. The heat exchangers 40,42 include a sealed, aluminum canister 44 similar or identical in construction to the aluminum canister employed in the MDI's 10. The internal geometry of the heat exchangers is preferably designed for turbulent flow therein. A liquid, preferably water, is supplied to the heat exchangers 40,42 from a supply feed line 46 (from a chiller which is not shown) to a non-conductive, flexible line 48 to an internal supply tube 50 fixedly or removably attached to the removable canister lid 52. The lid 52 is removable to inspect, clean, or repair the interior of the heat exchanger 40,42. An internal return tube 54 is similarly fixedly or removably attached to the lid 52. Cooling water is returned to the chiller (not shown) through a cooling return line 56 that also includes a nonconductive, flexible line 48'. In a linear configuration of objects, it is known in the art that induction heating efficiency is improved where each conductive object is proximate (preferably touching) to other conductive objects. This phenomenon is known as an electromagnetic effect inherent in induction heating. Thus, in this case, the first and last MDI's 10',10" are proximate to only one other MDI 10 whereas the other MDI's 10 are proximate to two other MDI's. It was determined that this electromagnetic effect reduced the induction heating efficiency of the first and iast MDI's 10', 10" such that ihey were 5C° cooler. This would be problematic since the FDA has required stress testing of all MDI's in the range of 55°C±5C°. The present invention overcomes this potential problem. The heat exchangers 40,42 are preferably employed to straddle the first and last MDI's 10', 10" (preferably 32 total MDI's) so that they are positioned proximate (touching or close) to the first and last MDI's during the heating cycle. During the induction heating cycle, the first and last MDI's 10'. 10" are heated sufficiently the same as the other MDI's because each MDI 10'.10* is proximate to another conductive MDI 10 and a respective canister 44 of each respective heat exchanger 40,42. The heat exchangers 40,42 are continuously or intermittently cooled with cooling water to control their temperature. Cooling is needed so that a more than insignificant amount of heat is not transferred to the first and last MD110', 10" by conductive and/or convection. Such non-induction forms of heat transfer may occur without cooling because the heat exchangers 40,42 are repetitively heated whereas the MDI's 10, 10',10" should be heated by induction only once. WE CLAIM: 1. An apparatus for heating metered dose inhalers comprising: an electrical power supply; one or more induction coils, wherein each of the one or more induction coils is present as a single, continuous coil in the shape of a loop having first and second bridges on the first and second ends of the loop, respectively, and wherein the first and second bridges are suitably sized and configured to directly heat each entire inhalation device; a conveyor; and a computer-controlled gating assembly for indexing a predetermined number of metered dose inhalers along the conveyor between the first and second bridges of the induction coil, the computer-controlled gating assembly having a non-conductive placement arm and wherein the metered dose inhalers comprise a first metered dose inhaler and a last metered dose inhaler, the computer-controlled gating assembly having first and second heat exchangers, suitably adapted and positioned to heat the first metered dose innaler and the last metered dose inhaler indexed within the one or more induction coils; wherein the first and second heat exchangers are employed to straddle the first metered dose inhaler and the last metered dose inhaler so that they are positioned proximate to the first metered dose inhaler and the last metered dose inhaler during a heating cycle. 2. The apparatus as claimed in Claim 1,' having) a microprocessor for controlling the power supply in the range of 100-130 amps to heat the inhalation devices to a temperature in the range of 50-60ºC. 3. The apparatus as claimed in Claim 2, having _ a cooling system having a condenser and a pump, wherein a liquid coolant is pumped through the induction coil, and wherein the electrical power supply has a maximum power output of 20 kilowatts and operates in the range of 80-90% efficiency. 4. The apparatus as claimed in Claim 2, wherein the power supply provides up to 20kva and 50-450 kHz, and wherein 140 volts Is applied to the one or more induction coils. 5. The apparatus as claimed in Ciaim 2, wherein the induction coil is constructed from copper tubing and silver soldered joints. 6. The apparatus as claimed in Claim 1, wherein the first and second heat exchangers each comprise an aluminum canister adapted to be cooled. 7. The apparatus as claimed in Claim 1, wherein the gating assembly is adapted to index 32 metered dose inhalers per heating cycle, wherein 4 slugs of 8 metered dose inhalers per slug are indexed each cycle, and wherein the cycle time is in the range of 30-40 seconds. 3, The apparatus as claimed in Claim 1, wherein the conveyor has a line speed in the range of 100-140 metered dose inhalers per minute. 9. The apparatus as claimed in Claim 1, having an infrared thermometer to measure the temperature of the metered dose inhalers. 10. The apparatus as claimed in Claim 9, wherein the measured temperatures are fed to a microprocessor, and wherein the microprocessor adjusts the power supply to heat the metered dose inhalers to a temperature of about 55°C. 11. The apparatus as claimed in Claim 10, having a weighing device to check the weight of the heated metered dose inhalers. An apparatus is claimed for heat stress testing of metered dose inhalers (10) to detect and reject non-conforming inhalers. The apparatus includes an electrical power supply (32) and one or more induction coils (24,26,28). The induction coil (24,26,28) is suitably sized and configured to directly heat each entire inhaler (10). A computer controlled gating assembly (22a, 22b, 22c) is included and contains first and second heat exchangers (40,42) employed to straddle a first metered dose inhaler (10') and a second metered dose inhaler (10") so that they are positioned proximate to these inhalers during the heating cycle. As a result of the proximate positioning, heating inefficiencies are reduced.

Documents:

1048-KOLNP-2003-FORM-27.pdf

1048-kolnp-2003-granted-abstract.pdf

1048-kolnp-2003-granted-assignment.pdf

1048-kolnp-2003-granted-claims.pdf

1048-kolnp-2003-granted-correspondence.pdf

1048-kolnp-2003-granted-description (complete).pdf

1048-kolnp-2003-granted-drawings.pdf

1048-kolnp-2003-granted-examination report.pdf

1048-kolnp-2003-granted-form 1.pdf

1048-kolnp-2003-granted-form 18.pdf

1048-kolnp-2003-granted-form 3.pdf

1048-kolnp-2003-granted-form 5.pdf

1048-kolnp-2003-granted-gpa.pdf

1048-kolnp-2003-granted-reply to examination report.pdf

1048-kolnp-2003-granted-specification.pdf