Claims for Patent: 11,110,094

Summary for Patent: 11,110,094

Title:	Risperidone sustained release microsphere composition
Abstract:	A risperidone sustained release microsphere formulation is provided. The microsphere formulation comprise risperidone or 9-hydroxy risperidone or salts thereof, and a polymer blend having a first uncapped lactide-glycolide copolymer and a second uncapped lactide-glycolide copolymer, in which the first uncapped lactide-glycolide copolymer is a copolymer with a high intrinsic viscosity and the second uncapped lactide-glycolide copolymer is a copolymer with a low intrinsic viscosity. The sustained release microsphere formulation according to an embodiment of the present disclosure is suitable for large-scale industrialized production with improved stability, the in vivo release behavior of which will not change after long-term storage.
Inventor(s):	Kaoxiang Sun, Rongcai Liang, Oilin Wang, Wenyan Wang, Wanhui Liu, Youxin Li
Assignee:	Luye Innomind Pharma Shijiazhuang Co Ltd
Application Number:	US16/525,502
Patent Claims:	1. A pharmaceutical composition comprising: a pharmaceutically active component selected from risperidone or a salt thereof, 9-hydroxy risperidone or a salt thereof; and a polymer blend consisting of a first uncapped poly(lactide-co-glycolide) and a second uncapped poly(lactide-co-glycolide), wherein the first uncapped poly(lactide-co-glycolide) has a molar ratio of lactide to glycolide of 65:35 to 90:10; and the second uncapped poly(lactide-co-glycolide) has a molar ratio of lactide to glycolide of 50:50 to 75:25; and wherein the pharmaceutical composition is prepared by forming a plurality of microspheres, each microspheres consisting of the pharmaceutically active component encapsulated in the polymer blend. 2. The pharmaceutical composition according to claim 1, wherein the second uncapped poly(lactide-co-glycolide) has a molar ratio of lactide to glycolide of 50:50. 3. The pharmaceutical composition according to claim 1, wherein forming the plurality of microspheres comprises the steps of: a) dissolving the active agent and the polymer blend in an organic solvent to form a mixture; b) combining the mixture with an aqueous solution comprising a water soluble polymer for emulsification; c) removing the organic solvent to provide a residue; d) washing and filtering the residue to obtain the microspheres. 4. The pharmaceutical composition according to claim 3, wherein a concentration of the polymer blend in the organic solvent is from 70mg/ml to 160mg/ml. 5. The pharmaceutical composition according to claim 4, wherein the concentration of the polymer blend in the organic solvent is from 80mg/ml to 140mg/ml. 6. The pharmaceutical composition according to claim 5, wherein the concentration of the polymer blend in the organic solvent is from 90mg/ml to 120mg/ml. 7. The pharmaceutical composition according to claim 6, wherein the concentration of the polymer blend in the organic solvent is 90mg/ml. 8. The pharmaceutical composition according to claim 3, wherein the mixture is combined with the aqueous solution through a homogenizer at a rotation speed of about 380 rpm. 9. The pharmaceutical composition according to claim 3, wherein the volume ratio between the organic solvent and the aqueous solution is 1:100. 10. The pharmaceutical composition according to claim 3, wherein the organic solvent is dichloromethane, and wherein the water soluble polymer is polyvinyl alcohol. 11. The pharmaceutical composition according to claim 4, wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.4-0.9 dl/g, and the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.35 dl/g. 12. The pharmaceutical composition according to claim 11 wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.45-0.8 dl/g; and the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.3 dl/g. 13. The pharmaceutical composition according to claim 12 wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.45-0.55 dl/g; and the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.2-0.3 dl/g. 14. The pharmaceutical composition according to claim 4, wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 50,000-145,000, and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 4,000-45,000. 15. The pharmaceutical composition according to claim 14 wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 55,000-110,000; and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 4,000-35,000. 16. The pharmaceutical composition according to claim 15 wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 55,000-85,000; and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 15,000-35,000. 17. The pharmaceutical composition according to claim 4, wherein the first uncapped poly(lactide-co-glycolide) is present in the polymer blend at 50-95 wt % and the second uncapped poly(lactide-co-glycolide) is present in the polymer blend at 5-50 wt %. 18. The pharmaceutical composition according to claim 17, wherein the first uncapped poly(lactide-co-glycolide) is present in the polymer blend at 70-90 wt % and the second uncapped poly(lactide-co-glycolide) is present in the polymer blend at 10-30 wt %. 19. The pharmaceutical composition according to claim 18, wherein the first uncapped poly(lactide-co-glycolide) is present in the polymer blend at 80 wt % and the second uncapped poly(lactide-co-glycolide) is present in the polymer blend at 20 wt %. 20. The pharmaceutical composition according to claim 4, wherein a weight content of the pharmaceutically active component in the microspheres is within a range from 10% to 60%; and a weight content of the polymer blend in the microspheres is within a range from 40% to 90%. 21. The pharmaceutical composition according to claim 20, wherein a weight content of the pharmaceutically active component in the microspheres is within a range of 35%-55%; and a weight content of the polymer blend in the microspheres is within a range of 45%-65%. 22. The pharmaceutical composition according to claim 21, wherein a weight content of the pharmaceutically active component in the microspheres is within a range of 40% -50%; and a weight content of the polymer blend in the microspheres is within a range of 50% -60%.