Claims for Patent: 10,792,262

Summary for Patent: 10,792,262

Title:	Stabilized formulations of 4-amino-3-substituted butanoic acid derivatives
Abstract:	Pharmaceutical compositions including an active ingredient and a stabilizer, as well as methods of manufacture of the compositions, and methods of their use.
Inventor(s):	Penake; David (Atlanta, GA), Hamm; Sharon (Odessa, FL), O'Mahony; Leonard (Westmeath, IE), Devane; John (Dublin, IE), Mohr; Wolfgang (Freiburg, DE), Weinheimer; Manuel (Neuenburg am Rhein, DE)
Assignee:	SAOL INTERNATIONAL LIMITED (Hamilton, BM)
Application Number:	16/524,664
Patent Claims:	1. A pharmaceutical composition, comprising: an active ingredient selected from 4-amino-3-(4-chlorophenyl)butanoic acid) ("baclofen") and its pharmaceutically acceptable salts; and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate) ("stabilizer"); wherein a weight ratio of the stabilizer to the active ingredient is from 1.5:1 to 10:1 and wherein the active ingredient and stabilizer are present in a matrix. 2. The composition of claim 1, wherein the active ingredient is dispersed throughout a matrix of the stabilizer. 3. The composition of claim 2, wherein the active ingredient and the stabilizer are intimately mixed in a matrix formulation. 4. The composition of claim 1, wherein the weight ratio of the stabilizer to the active ingredient is from 1.8:1 to 7.2:1. 5. The pharmaceutical composition of claim 4, further comprising one or more excipients selected from xylitol, calcium stearate, colloidal silicon dioxide, talc, and flavoring. 6. The composition according to claim 4, further comprising a saliva-forming agent. 7. The composition of claim 1, further comprising an excipient. 8. The pharmaceutical composition of claim 7, wherein the excipient comprises one or more glidants, lubricants, fillers, sweeteners, taste-masking agents, disintegrants, saliva-forming agents, binding agents, or flavorings. 9. The composition of claim 8, wherein the at least one excipient is xylitol, mannitol, saccharin sodium, hypromellose, crospovidone, calcium stearate, colloidal silicon dioxide, talc, or flavoring. 10. The pharmaceutical composition of claim 1, wherein the composition is in a solid dosage form. 11. A method of making the composition of claim 1, comprising intimately mixing together the active ingredient and stabilizer. 12. The method according to claim 11, wherein the intimately mixing comprises at least one of wet granulation and dry granulation. 13. The method according to claim 12, comprising wet granulation, wherein the wet granulation comprises dry blending the active ingredient and stabilizer, then adding a solvent, and granulating the mixture. 14. The method according to claim 11, wherein the intimately mixing comprises dry blending. 15. The method according to claim 11, further comprising dry compacting or slugging to form a solid dosage form. 16. The method according to claim 15, further comprising coating the solid dosage form. 17. A method of treating spasticity, comprising administering to a patient in need thereof an effective amount of the composition of claim 1. 18. A method of reducing lactam formation in a baclofen formulation, the method comprising intimately mixing together baclofen or a pharmaceutically acceptable salt thereof and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate) ("stabilizer"); wherein a weight ratio of the stabilizer to the baclofen or a pharmaceutically acceptable salt thereof is from 1.5:1 to 10:1. 19. The method according to claim 18, wherein the baclofen is micronized. 20. The method according to claim 18, further comprising milling the baclofen to reduce its particle size before intimately mixing with the stabilizer. 21. A method of increasing the shelf life of a solid baclofen formulation, the method comprising: reducing formation of 4-(4-chlorophenyl)-2-pyrrolidine (4-CPP) in a baclofen formulation by intimately mixing together baclofen or a pharmaceutically acceptable salt thereof and a poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate) ("stabilizer") to form a solid baclofen formulation; wherein a weight ratio of the stabilizer to the baclofen or a pharmaceutically acceptable salt thereof is from 1.5:1 to 10:1. 22. The method according to claim 21, wherein an amount of 4-CPP in the solid baclofen formulation increases by no more than 0.2% after six months of stability testing at 40.degree. C., 75% relative humidity. 23. The method according to claim 22, wherein an amount of 4-CPP in the solid baclofen formulation increases by no more than 0.1% after six months of stability testing at 40.degree. C., 75% relative humidity.