Sustained delivery formulations of risperidone compound
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 pharmaceutical composition comprising risperidone base in a solution which comprises:
(i) an 80/20 poly(DL-lactide-co-glycolide) copolymer having a carboxy terminal group, and
(ii) N-methyl-2-pyrrolidone, 2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, propylene carbonate, caprolactam, triacetin, ethanol, glycerin, propylene glycol, butanol, acetone, diethyl ketone, methyl ethyl ketone, 2-ethoxyethyl acetate, ethyl acetate, methyl acetate, ethyl lactate, ethyl butyrate, diethyl malonate, diethyl glutaconate, tributyl citrate, diethyl succinate, tributyrin, isopropyl myristate, dimethyl adipate, dimethyl succinate, dimethyl oxalate, dimethyl citrate, triethyl citrate, acetyl tributyl citrate, glyceryl triacetate, dimethylacetamide, tetrahydrofuran, solketal, oleic acid, 1-dodecylazacycloheptan-2-one, ethylene carbonate, dimethyl carbonate, glycerol formal, glycofurol, dimethyl sulfone, epsilon-caprolactone, butyrolactone, diacetin, N,N-dimethyl-m-toluamide, benzyl alcohol, benzyl benzoate, dipropylene glycol, ethyl oleate, isopropyl myristate, isopropyl palmitate, oleic acid, polyethylene glycol, or a combination of two or more thereof.
2. The composition of claim 1 , wherein (ii) comprises dimethyl sulfoxide.
3. The composition of claim 1 , wherein (ii) comprises N-methyl-2-pyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, acetone, ethyl acetate, tributyl citrate, diethyl succinate, triethyl citrate, acetyl tributyl citrate, glyceryl triacetate, dimethylacetamide, epsilon-caprolactone, or a combination of two or more thereof.
4. The composition of claim 1 , wherein the composition comprises about 90 mg or about 120 mg of risperidone base.
5. The method of claim 1 , wherein the method provides steady-state risperidone plasma levels from four to six weeks.
6. The composition of claim 1 , wherein the composition comprises about 10 wt % to about 50 wt % of the risperidone base.
7. The composition of claim 6 , wherein the composition comprises about 10 wt % to about 30 wt % of the risperidone base.
8. The composition of claim 7 , wherein the composition comprises about 10 wt % to about 20 wt % of the risperidone base.
9. The composition of claim 8 , wherein the composition comprises about 15 wt % of the risperidone base.
10. The composition of claim 9 , wherein the solution comprises about 45 wt % of (i) and about 55 wt % of (ii).
11. The composition of claim 1 , wherein the solution comprises about 10 wt % to about 70 wt % of (i) and about 10 wt % to about 70 wt % of (ii).
12. The composition of claim 11 , wherein the solution comprises about 20 wt % to about 70 wt % of (i) and about 30 wt % to about 70 wt % of (ii).
13. The composition of claim 12 , wherein the solution comprises about 40 wt % to about 50 wt % of (i) and about 50 wt % to about 60 wt % of (ii).
14. The composition of claim 1 , wherein the copolymer has an average molecular weight from about 10,000 Daltons to about 45,000 Daltons.
15. The composition of claim 14 , wherein the copolymer has an average molecular weight from about 15,000 Daltons to about 40,000 Daltons.
16. A method of treating schizophrenia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 1 .
17. The method of claim 16 , comprising subcutaneously injecting the subject with the composition once per month.
18. The method of claim 16 , wherein the composition comprises about 30 mg of risperidone base.
19. The method of claim 16 , wherein the composition comprises about 60 mg of risperidone base.
20. The method of claim 16 , wherein the composition comprises about 90 mg of risperidone base.
21. The method of claim 16 , wherein the composition comprises about 120 mg of risperidone base.
22. The method of claim 16 , wherein the composition comprises about 180 mg of risperidone base.
23. The method of claim 16 , wherein the composition comprises from about 3 mg to about 300 mg of risperidone base.
24. The method of claim 16 , wherein the composition comprises from about 9 mg to about 900 mg of risperidone base.
25. The method of claim 16 , wherein the subject is not administered a supplemental daily oral dose of risperidone.
26. The method of claim 16 , 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.
27. The method of claim 16 , wherein the method provides therapeutic plasma risperidone levels immediately after injection.
28. A method of treating a mental condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 1 ; wherein the mental condition is schizophrenia, bipolar disorder, obsessive-compulsive disorder, Tourette syndrome, or an autistic spectrum disorder.
29. The method of claim 28 , wherein the mental condition is bipolar disorder.
30. The method of claim 28 , wherein the mental condition is autistic spectrum disorder.