Claims for Patent: 8,980,319

Summary for Patent: 8,980,319

Title:	Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
Abstract:	Methods for producing stabilized solid dosage form pharmaceutical compositions are provided. In particular, methods for preparing protected granules containing morphinans, and solid dosage form pharmaceutical compositions produced using the morphinan-protected granules are provided.
Inventor(s):	Park; Jae Han (Olivette, MO), Eisenhauer; Tiffani (Columbia, IL), Dhanarajan; Anish (Metuchen, NJ), Gupta; Vishal (Hillsborough, NJ), Overholt; Stephen (Middlesex, NJ)
Assignee:	Mallinckrodt LLC (Hazelwood, MO)
Application Number:	14/092,375
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,980,319
Patent Claims:	1. A solid dosage pharmaceutical composition comprising: (a) a plurality of granules containing a pharmaceutically acceptable salt of oxycodone, wherein the granules are substantially resistant to oxidative degradation of the pharmaceutically acceptable salt of oxycodone; and (b) an additional active ingredient, wherein the granules comprise an interior region substantially comprising the pharmaceutically acceptable salt of oxycodone and an exterior region substantially comprising at least one excipient; wherein the granule contains less than about 0.5% w/w of the total mass of the pharmaceutically acceptable salt of oxycodone of each of any one or more of a degradant selected from 10-hydroxy oxycodone, di-hydroxy oxycodone, and oxycodone N-oxide after being stored for 6 months at 40.degree. C. and 75% relative humidity. 2. A solid dosage pharmaceutical composition of claim 1, wherein the additional active ingredient is acetaminophen. 3. A solid dosage pharmaceutical composition of claim 1, wherein the at least one excipient is chosen from the group consisting of a binder, a filler, an antioxidant, a chelating agent, and combinations thereof. 4. A solid dosage pharmaceutical composition of claim 1, further comprising at least one additional excipient selected from the group consisting of pH adjusting agents, antimicrobial agents, and combinations thereof. 5. A solid dosage pharmaceutical composition of claim 1, wherein the composition further comprises microcrystalline cellulose, pregelatinized starch, Na.sub.2EDTA, and citric acid. 6. A solid dosage pharmaceutical composition of claim 1, wherein the composition further comprises a hydrophilic polymer. 7. A solid dosage pharmaceutical composition of claim 6, wherein the hydrophilic polymer is selected from the group consisting of cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose ethers, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, nitrocellulose, crosslinked starch, agar, casein, chitin, collagen, gelatin, maltose, mannitol, maltodextrin, pectin, pullulan, sorbitol, xylitol, polysaccharides, ammonia alginate, sodium alginate, calcium alginate, potassium alginate, propylene glycol alginate, alginate sodium carmellose, calcium carmellose, carrageenan, fucoidan, furcellaran, arabicgum, carrageensgum, ghaftigum, guargum, karayagum, locust beangum, okragum, tragacanthgum, scleroglucangum, xanthangum, hypnea, laminaran, acrylic polymers, acrylate polymers, carboxyvinyl polymers, copolymers of maleic anhydride and styrene, copolymers of maleic anhydride and ethylene, copolymers of maleic anhydride propylene or copolymers of maleic anhydride isobutylene, crosslinked polyvinyl alcohol and poly N-vinyl-2-pyrrolidone, diesters of polyglucan, polyacrylamides, polyacrylic acid, polyamides, polyethylene glycols, polyethylene oxides, poly(hydroxyalkyl methacrylate), polyvinyl acetate, polyvinyl alcohol, polyvinyl chloride, polystyrenes, polyvinylpyrrolidone, anionic and cationic hydrogels, and combinations thereof. 8. A solid dosage pharmaceutical composition of claim 1, wherein the composition further comprises a hydrophobic polymer. 9. A solid dosage pharmaceutical composition of claim 8, wherein the hydrophobic polymer is selected from the group consisting of cellulose acetate butyrate, cellulose acetate ethylcarbamate, cellulose acetate heptanoate, cellulose acetate methylcarbamate, cellulose acetate octanoate, cellulose acetate phthalate, cellulose acetate propionate, cellulose acetate succinate, cellulose acetate trimaletate, cellulose acetaldehyde dimethyl acetate, cellulose butyrate, cellulose dimethylaminoacetate, cellulose disuccinate, cellulose dipalmitate, cellulose dicaprylate, cellulose propionate, cellulose propionate succinate, cellulose trioctanoate, cellulose tripropionate, cellulose trimellitate, cellulose tripalmitate, cellulose trivalerate, cellulose valerate palmitate, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, ethylhydroxy ethylcellulose, hydroxy propyl methylcellulose phthalate, methyl cellulose, methyl ethyl cellulose, propyl cellulose, sodium carboxymethyl starch, polyvinyl acetate phthalate, polyvinyl alcohol phthalate, methacrylic acid copolymers, methacrylic acid ester copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylate), poly(methacrylate), poly(methyl methacrylate), poly(ethylacrylate), poly(ethyl methacrylate), poly(methacrylic acid anhydride), glycidyl methacrylate copolymers, ammonio methacrylate copolymers, lecithins, aluminum monostearate, cetylalcohol, hydrogenated beef tallow, hydrogenated castor oil, hydrogenated vegetable oil, 12-hydroxystearyl alcohol, glyceryl monopalmitate, glyceryl dipalmitate, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, myristyl alcohol, stearic acid, stearyl alcohol, polyethyleneglycols, zein, shellac, bee's wax, carnauba wax, glyceryl behenate, Japan wax, paraffin, spermaceti, synthetic waxes, and combinations thereof. 10. A solid dosage pharmaceutical composition of claim 1, wherein the composition is a bilayer tablet. 11. A solid dosage pharmaceutical composition comprising: (a) an immediate release layer; and (b) a sustained release layer, wherein both the immediate release layer and the sustained release layer comprise a plurality of granules containing a pharmaceutically acceptable salt of oxycodone, wherein the granules containing the pharmaceutically acceptable salt of oxycodone comprise an interior region substantially comprising the pharmaceutically acceptable salt of oxycodone and an exterior region substantially comprising at least one excipient, wherein the granule contains less than about 0.5% w/w of the total mass of the pharmaceutically acceptable salt of oxycodone of each of any one or more of a degradant selected from 10-hydroxy oxycodone, di-hydroxy oxycodone, and oxycodone n-oxide after being stored for 6 months at 40.degree. C. and 75% relative humidity. 12. A solid dosage pharmaceutical composition of claim 11, wherein the at least one excipient is chosen from the group consisting of a binder, a filler, an antioxidant, a chelating agent, and combinations thereof. 13. A solid dosage pharmaceutical composition of claim 11, further comprising at least one additional excipient selected from the group consisting of pH adjusting agents, antimicrobial agents, and combinations thereof. 14. A solid dosage pharmaceutical composition of claim 11, wherein the at least one excipient is chosen from the group consisting of microcrystalline cellulose, pregelatinized starch, Na.sub.2EDTA, and citric acid. 15. A solid dosage pharmaceutical composition of claim 11, wherein the composition further comprises a hydrophilic polymer. 16. A solid dosage pharmaceutical composition of claim 15, wherein the hydrophilic polymer is polyethylene oxide. 17. A solid dosage pharmaceutical composition of claim 11, wherein the composition further comprises an additional active ingredient. 18. A solid dosage pharmaceutical composition of claim 17, wherein the additional active ingredient is acetaminophen. 19. A solid dosage pharmaceutical composition comprising: (a) a plurality of granules containing a pharmaceutically acceptable salt of hydrocodone, wherein the granules are substantially resistant to oxidative degradation of hydrocodone; and (b) an additional active ingredient, wherein the granules containing the pharmaceutically acceptable salt of hydrocodone comprise an interior region substantially comprising the pharmaceutically acceptable salt of hydrocodone and an exterior region substantially comprising at least one excipient; wherein the granule contains less than about 0.5% w/w of the total mass of the pharmaceutically acceptable salt of hydrocodone of each of any one or more of a degradant selected from hydrocodone-N-oxide and hydrocodone aldol dimer after being stored for 6 months at 40.degree. C. and 75% relative humidity. 20. A solid dosage pharmaceutical composition of claim 19, wherein the additional active ingredient is acetaminophen. 21. A solid dosage pharmaceutical composition of claim 19, wherein the at least one excipient is chosen from the group consisting of a binder, a filler, an antioxidant, a chelating agent, and combinations thereof. 22. A solid dosage pharmaceutical composition of claim 19, further comprising at least one additional excipient selected from the group consisting of pH adjusting agents, antimicrobial agents, and combinations thereof. 23. A solid dosage pharmaceutical composition of claim 19, wherein the composition further comprises microcrystalline cellulose, pregelatinized starch, Na.sub.2EDTA, and citric acid. 24. A solid dosage pharmaceutical composition of claim 19, wherein the composition further comprises a hydrophilic polymer. 25. A solid dosage pharmaceutical composition of claim 19, wherein the composition further comprises a hydrophobic polymer. 26. A solid dosage pharmaceutical composition of claim 19, wherein the composition is a bilayer tablet. 27. A solid dosage pharmaceutical composition comprising: (a) an immediate release layer; and (b) a sustained release layer, wherein both the immediate release layer and the sustained release layer comprise a plurality of granules containing a pharmaceutically acceptable salt of hydrocodone, wherein the granules containing the pharmaceutically acceptable salt of hydrocodone comprise an interior region substantially comprising the pharmaceutically acceptable salt of hydrocodone and an exterior region substantially comprising at least one excipient, wherein the granule contains less than about 0.5% w/w of the total mass of the pharmaceutically acceptable salt of hydrocodone of each of any one or more of a degradant selected from hydrocodone-n-oxide and hydrocodone aldol dimer after being stored for 6 months at 40.degree. C. and 75% relative humidity. 28. A solid dosage pharmaceutical composition of claim 27, wherein the at least one excipient is chosen from the group consisting of a binder, a filler, an antioxidant, a chelating agent, and combinations thereof. 29. A solid dosage pharmaceutical composition of claim 27, wherein the composition further comprises an additional active ingredient. 30. A solid dosage pharmaceutical composition of claim 29, wherein the additional active ingredient is acetaminophen.