Sustained delivery formulations of risperidone compound
View Patent ↗The present invention relates to a risperidone sustained release delivery system for treatment of medical conditions relating to delusional psychosis, schizophrenia, bipolar disorder, psychotic depression, obsessive-compulsion disorder, Tourette syndrome, and autistic spectrum disorders. The sustained release delivery system includes a flowable composition containing risperidone, a metabolite, or a prodrug thereof and an implant containing risperidone, a metabolite, or a prodrug thereof. The flowable composition may be injected into tissue whereupon it coagulates to become a solid or gel, monolithic implant. The flowable composition includes a biodegradable, thermoplastic polymer, an organic liquid, and risperidone, a metabolite or a prodrug thereof.
1. A method of treating schizophrenia in a subject in need thereof, the method comprising subcutaneously injecting the subject with a composition comprising risperidone base in a solution comprising: (i) an 80/20 poly(DL-lactide-co-glycolide) copolymer having a carboxy terminal group, and (ii) N-methyl-2-pyrrolidone; to treat the schizophrenia.
2. The method of claim 1 , comprising subcutaneously injecting the subject with the composition once every twenty-eight days.
3. The method of claim 1 , comprising subcutaneously injecting the subject with the composition once per month.
4. The method of claim 1 , wherein the composition comprises about 10 wt % to about 50 wt % of the risperidone base.
5. The method of claim 1 , wherein the composition comprises about 10 wt % to about 30 wt % of the risperidone base.
6. The method of claim 1 , wherein the composition comprises about 10 wt % to about 20 wt % of the risperidone base.
7. The method of claim 1 , wherein the solution comprises: (i) about 10 wt % to about 70 wt % of the 80/20 poly(DL-lactide-co-glycolide) copolymer having a carboxy terminal group, and (ii) about 10 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
8. The method of claim 1 , wherein the solution comprises: (i) about 20 wt % to about 70 wt % of the 80/20 poly(DL-lactide-co-glycolide) copolymer having a carboxy terminal group, and (ii) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
9. The method of claim 1 , wherein the solution comprises: (i) about 40 wt % to about 50 wt % of the 80/20 poly(DL-lactide-co-glycolide) copolymer, and (ii) about 50 wt % to about 60 wt % of N-methyl-2-pyrrolidone.
10. The method of claim 1 , wherein the copolymer has an average molecular weight from about 10,000 Daltons to about 45,000 Daltons.
11. The method of claim 1 , wherein the copolymer has an average molecular weight from about 15,000 Daltons to about 40,000 Daltons.
12. The method of claim 1 , wherein the composition comprises about 90 mg of risperidone base.
13. The method of claim 1 , wherein the composition comprises about 120 mg of risperidone base.
14. The method of claim 1 , wherein the subject is not administered a supplemental daily oral dose of risperidone.
15. The method of claim 1 , wherein the subject is not administered a supplemental daily oral dose of risperidone for the first twenty-one days of the method of treating schizophrenia.
16. The method of claim 1 , wherein the method provides therapeutic plasma risperidone levels immediately after injection.
17. The method of claim 1 , wherein the method provides steady-state risperidone plasma levels from four to six weeks.
18. The method of claim 1 , wherein the composition comprises about 30 mg of risperidone base.
19. The method of claim 1 , wherein the composition comprises about 60 mg of risperidone base.
20. The method of claim 1 , wherein the composition comprises about 180 mg of risperidone base.
21. The method of claim 1 , wherein the composition comprises from about 3 mg to about 300 mg of risperidone base.
22. The method of claim 1 , wherein the composition comprises from about 9 mg to about 900 mg of risperidone base.
23. The method of claim 1 , wherein the composition comprises about 15 wt % of the risperidone base in a solution comprising: (i) about 45 wt % of the 80/20 poly(DL-lactide-co-glycolide) copolymer, and (ii) about 55 wt % of N-methyl-2-pyrrolidone.
24. The method of claim 23 , wherein the subject is not administered a supplemental daily oral dose of risperidone.
25. The method of claim 23 , wherein the subject is not administered a supplemental daily oral dose of risperidone for the first twenty-one days of the method of treating schizophrenia.
26. The method of claim 23 , wherein the method provides therapeutic plasma risperidone levels immediately after injection.
27. The method of claim 23 , wherein the method provides steady-state risperidone plasma levels from four to six weeks.
28. The method of claim 23 , wherein the composition comprises about 30 mg of risperidone base.
29. The method of claim 23 , wherein the composition comprises about 60 mg of risperidone base.
30. The method of claim 23 , wherein the composition comprises about 180 mg of risperidone base.
31. The method of claim 23 , wherein the composition comprises from about 3 mg to about 300 mg of risperidone base.
32. The method of claim 23 , wherein the composition comprises from about 9 mg to about 900 mg of risperidone base.
33. A method of treating schizophrenia in a subject in need thereof, the method comprising subcutaneously injecting the subject with a composition comprising about 10 wt % to about 30 wt % risperidone base in a solution comprising: (i) about 10 wt % to about 70 wt % of an 80/20 poly(DL-lactide-co-glycolide) copolymer having a carboxy terminal group, and (ii) about 10 wt % to about 70 wt % of N-methyl-2-pyrrolidone; to treat the schizophrenia.
34. The method of claim 33 , comprising subcutaneously injecting the subject with the composition once per month.
35. The method of claim 33 , wherein the composition comprises about 90 mg of risperidone base.
36. The method of claim 33 , wherein the composition comprises about 120 mg of risperidone base.
37. The method of claim 33 , wherein the subject is not administered a supplemental daily oral dose of risperidone.
38. The method of claim 33 , wherein the subject is not administered a supplemental daily oral dose risperidone for the first twenty-one days of the method of treating schizophrenia.
39. The method of claim 33 , wherein the method provides therapeutic plasma risperidone levels immediately after injection.
40. The method of claim 33 , wherein the method provides steady-state risperidone plasma levels from four to six weeks.
41. The method of claim 33 , wherein the composition comprises about 30 mg of risperidone base.
42. The method of claim 33 , wherein the composition comprises about 60 mg of risperidone base.
43. The method of claim 33 , wherein the composition comprises about 180 mg of risperidone base.
44. The method of claim 33 , wherein the composition comprises from about 3 mg to about 300 mg of risperidone base.
45. The method of claim 33 , wherein the composition comprises from about 9 mg to about 900 mg of risperidone base.