Sustained release small molecule drug formulation
An injectable depot formulation includes a biocompatible polymer, an organic solvent combined with the biocompatible polymer to form a viscous gel, and a small molecule drug incorporated in the viscous gel such that the formulation exhibits an in vivo release profile having a C max to C min ratio of less than 200 and a lag time less than 0.2.
1. An injectable pharmaceutical composition comprising from about 10 wt % to about 30 wt % of risperidone base suspended in a gel comprising: (i) from about 40 wt % to about 60 wt % of a copolymer of lactic acid and glycolic acid, wherein the lactic acid to glycolic acid monomer ratio is from about 100:0 to about 60:40, and wherein the copolymer has a number average molecular weight from about 5,000 Daltons to about 30,000 Daltons, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof.
2. The composition of claim 1 , wherein the gel consists of (i) and (ii).
3. An injectable pharmaceutical composition comprising from about 1 wt % to about 50 wt % of risperidone base suspended in a gel comprising: (i) from about 5 wt % to about 80 wt % of a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof.
4. The composition of claim 3 , comprising from about 5 wt % to about 40 wt % of risperidone base.
5. The composition of claim 4 , comprising from about 5 wt % to about 30 wt % of risperidone base.
6. The composition of claim 5 , comprising from about 10 wt % to about 30 wt % of risperidone base.
7. The composition of claim 3 , wherein the gel comprises: (i) from about 20 wt % to about 70 wt % of a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof.
8. The composition of claim 7 , wherein the gel comprises: (i) from about 40 wt % to about 60 wt % of a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof.
9. The composition of claim 3 , wherein the lactic acid to glycolic acid monomer ratio in the copolymer is from about 100:0 to 60:40.
10. The composition of claim 9 , wherein the lactic acid to glycolic acid monomer ratio in the copolymer is from about 100:0 to 75:25.
11. The composition of claim 3 , wherein the copolymer has a number average molecular weight from about 1,000 Daltons to about 120,000 Daltons.
12. The composition of claim 11 , wherein the copolymer has a number average molecular weight from about 5,000 Daltons to about 30,000 Daltons.
13. The composition of claim 3 , wherein the gel consists of (i) and (ii).
14. An injectable pharmaceutical composition comprising risperidone base suspended in a gel comprising: (i) a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof.
15. A method of administering risperidone base to a subject in need thereof, the method comprising subcutaneously injecting the composition of claim 1 into the subject once per month.
16. A method of administering risperidone base to a subject in need thereof, the method comprising subcutaneously injecting the composition of claim 3 into the subject once per month.
17. A method of administering risperidone base to a subject in need thereof, the method comprising subcutaneously injecting the composition of claim 14 into the subject once per month.
18. A syringe comprising the composition of claim 1 .
19. A syringe comprising the composition of claim 3 .
20. A syringe comprising the composition of claim 14 .