Claims for Patent: 8,252,331

Summary for Patent: 8,252,331

Title:	Osmotic device containing amantadine and an osmotic salt
Abstract:	The osmotic devices of the present invention contain a unitary core comprising a salt of amantadine and an osmotic salt, wherein the two salts have an ion in common. The release rate of the amantadine is modified from a first order release profile to a zero order, pseudo-zero order or sigmoidal release profile by increasing the amount of the osmotic salt in the core of the device. The osmotic device includes a semipermeable membrane having a controlled porosity that can be adapted as needed to cooperate with the osmotic salt in providing a predetermined drug release profile. The osmotic salt need not be coated and it is in admixture with the amantadine salt.
Inventor(s):	Meyer; Glenn A. (Wilmington, NC), Feleder; Ethel C. (Buenos Aires, AR), Ricci; Marcelo A. (Buenos Aires, AR), Coppari; Marcelo A. (Buenos Aires, AR), Befumo; Marcelo F. (Buenos Aires, AR), Faour; Joaquina (Buenos Aires, AR), Vergez; Juan A. (Buenos Aires, AR)
Assignee:	Osmotica Kereskedelmi es Szolgaltato, KFT (Budapest, HU)
Application Number:	11/287,882
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,252,331
Patent Claims:	1. An osmotic device having a unitary core surrounded by a semipermeable membrane having at least one passageway there through, wherein: a) the unitary core comprises a mixture of amantadine salt, osmotic salt, and at least one other pharmaceutically acceptable excipient, wherein the amantadine salt is amantadine hydrochloride and the osmotic salt is sodium chloride, and the weight ratio of amantadine salt to osmotic salt ranges from 2:1 to 30:1; b) the osmotic salt is not coated with a release rate controlling coating; c) the permeability of the semipermeable membrane is adapted to cooperate with the osmotic salt to control the release profile of amantadine salt from the osmotic device; d) the amantadine salt and osmotic salt have an ion in common; e) amantadine salt is released through the one or more passageways according to a sigmoidal controlled release profile, optionally wherein release of amantadine salt is delayed for a period of time, when the osmotic device is exposed to an aqueous environment of use; and f) the semipermeable membrane comprises a cellulose acetate grade 1 and a cellulose acetate grade 2, wherein the weight ratio of a cellulose acetate of high viscosity to the total amount of cellulose acetates ranges from 0:1 to 1:1, the cellulose acetates grade 1 has 7-10% by wt of hydroxyl groups, 30-36% by wt. of acetyl groups and a viscosity of 200-280 seconds, the cellulose acetate grade 2 has 3-5% by weight of hydroxyl groups, 37-43% by wt. of acetyl groups and a viscosity of 6.0-45.0 seconds, the unitary core comprises less than 6% of NaCl w/w based upon the weight of the uncoated core, and the semipermeable membrane comprises more than 25% w/w of cellulose acetate grade 1 based upon the weight of the semipermeable membrane. 2. The osmotic device of claim 1 further comprising an external coat comprising an active drug. 3. The osmotic device of claim 2, wherein the active drug is an antidepressant. 4. The osmotic device of claim 3, wherein the antidepressant is citalopram. 5. The osmotic device of claim 2, wherein the active drug is an anxiolytic agent. 6. The osmotic device of claim 5, wherein the anxiolytic agent is buspirone. 7. The osmotic device of claim 1, further comprising a second active drug in the core. 8. The osmotic device of claim 7, wherein the second active drug is an anti-Parkinson drug. 9. The osmotic device of claim 8, wherein the second anti-Parkinson drug is selected from the group consisting of ropinirole, selegiline, and levodopa-carbidopa. 10. The osmotic device of claim 9, wherein the second anti-Parkinson drug is ropinirole. 11. The osmotic device of claim 9, wherein the second anti-Parkinson drug is selegiline. 12. The osmotic device of claim 9, wherein the second anti-Parkinson drug is levodopa-carbidopa. 13. The osmotic device of claim 1, wherein: the amantadine hydrochloride is released according to a sigmoidal release profile from the core as follows: TABLE-US-00017 Time (hours) Amount Released 0-3 Not less than 5% 0-5 Not less than 18% 0-8 Not less than 39% 0-16 Not less than 76%. 14. The osmotic device of claim 13, wherein the weight ratio of amantadine salt to osmotic salt ranges from 4:1 to 30:1, the semipermeable membrane comprises a weight ratio of cellulose acetate grade 1 to the total amount of cellulose acetates ranging from 0.3:1 to 0.7:1. 15. The osmotic device of claim 14, wherein the bioavailability is greater than 87%, compared to the immediate release dosage form of the same dose. 16. The osmotic device of claim 13 comprising: TABLE-US-00018 Ingredient Amount (mg) Core Amantadine HCl 100 A First Diluent 7-35 Binder 3-10 Glidant 0.1-2 Lubricant 0.3-3 Sodium Chloride 3.33-50 A Second Diluent 3-20 First Coating Cellulose acetate grade 1 0-20 Cellulose acetated grade 2 0-20 Plasticizer 0.2-1 17. The osmotic device of claim 13 comprising: TABLE-US-00019 Ingredient Amount (mg) Core Amantadine HCl 150 A First Diluent 10-55 Binder 4.5-15 Glidant 0.2-3 Lubricant 0.5-5 Sodium Chloride 5-75 A Second Diluent 4.5-30 First Coating Cellulose acetate grade 1 0-25 Cellulose acetate grade 2 0-25 Plasticizer 0.3-2 18. The osmotic device of claim 13 comprising: TABLE-US-00020 Ingredient Amount (mg) Core Amantadine HCl 300 A First Diluent 20-100 Binder 10-30 Glidant 0.2-5 Lubricant 1-7 Sodium Chloride 10-150 A Second Diluent 10-60 First Coating Cellulose acetate grade 1 0-50 Cellulose acetate grade 2 0-50 Plasticizer 0.5-3 19. The osmotic device of claim 1, wherein the amantadine is released according to the following profile: TABLE-US-00021 Performance Performance Time Minimum Maximum (hrs) (%) (%) 1 0 4 3 16 27 5 35 59 8 55 83 12 77 100 16 84 100 24 86 100. 20. An osmotic device having a unitary core surrounded by a semipermeable membrane having at least one passageway there through, wherein: a) the unitary core comprises a mixture of amantadine salt, osmotic salt, and at least one other pharmaceutically acceptable excipient; b) the amantadine salt and osmotic salt have an ion in common; c) the weight ratio of amantadine salt to osmotic salt is in the range of 30:1 to 2:1; d) the semipermeable membrane comprises 1.7% -15.0% of a plasticizer, 33.3% -61.2% of cellulose acetate grade 1 and 33.3% -61.2% of cellulose acetate grade 2, wherein the cellulose acetates grade 1 has 7-10% by wt of hydroxyl groups, 30-36% by wt. or acetyl groups and a viscosity of 200-280 seconds, and the cellulose acetate grade 2 has 3-5% by weight of hydroxyl groups, 37-43% by wt. or acetyl groups and a viscosity of 6.0-45.0 seconds; e) the unitary core comprises less than 6% of NaCl w/w based upon the weight of the uncoated core; and f) amantadine salt is released through the one or more passageways according to a sigmoidal release profile when the osmotic device is exposed to an aqueous environment of use.