Sustained release small molecule drug formulation
View Patent ↗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 C max to C min ratio less than 200 and lag time less than 0.2.
1. A method of administering risperidone base to a subject, comprising:
implanting in the subject a formulation comprising:
a copolymer of lactic acid and glycolic acid having a number average molecular weight ranging from 1000 Daltons to 30,000 Daltons;
an organic solvent combined with the copolymer to form a viscous gel, the organic solvent comprising N-methyl-2-pyrrolidone; and
risperidone base in particle form incorporated in the viscous gel,
wherein the copolymer and the N-methyl-pyrrolidone comprise a vehicle, the copolymer is present in the vehicle in an amount ranging from 40% to 55% by weight, and the organic solvent is present in the vehicle in an amount ranging from 45% to 60% by weight.
2. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from about 100:0 to 60:40.
3. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 100:0 to 75:25.
4. The method of claim 1 , wherein the copolymer has a number average molecular weight ranging from 5000 Daltons to 30,000 Daltons.
5. The method of claim 1 , wherein the organic solvent consists of N-methyl-2-pyrrolidone.
6. The method of claim 1 , wherein the risperidone base is present in the formulation in an amount ranging from 5 wt % to 40 wt %.
7. The method of claim 1 , wherein the risperidone base is present in the formulation in an amount ranging from 10 wt % to 30 wt %.
8. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from about 100:0 to 60:40, and the copolymer has a number average molecular weight ranging from 5000 Daltons to 30,000 Daltons.
9. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 100:0 to 75:25, and the copolymer has a number average molecular weight ranging from 5000 Daltons to 30,000 Daltons.
10. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from about 100:0 to 60:40, and the organic solvent consists of N-methyl-2-pyrrolidone.
11. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 100:0 to 75:25, the copolymer has a number average molecular weight ranging from 5000 Daltons to 30,000 Daltons, and the organic solvent consists of N-methyl-2-pyrrolidone.
12. The method of claim 1 , wherein the organic solvent consists of N-methyl-2-pyrrolidone, and the risperidone base is present in the formulation in an amount ranging from 10 wt % to 30 wt %.
13. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from about 100:0 to 60:40, the organic solvent consists of N-methyl-2-pyrrolidone, and the risperidone base is present in the formulation in an amount ranging from 10 wt % to 30 wt %.
14. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 100:0 to 75:25, the copolymer has a number average molecular weight ranging from 5000 Daltons to 30,000 Daltons, the organic solvent consists of N-methyl-2-pyrrolidone, and the risperidone base is present in the formulation in an amount ranging from 10 wt % to 30 wt %.
15. The method of claim 1 , wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 100:0 to 75:25, the organic solvent consists of N-methyl-2-pyrrolidone, and the risperidone base is present in the formulation in an amount ranging from 10 wt % to 30 wt %.
16. The method of claim 1 , wherein the formulation exhibits a lag time less than 0.2.
17. The method of claim 1 , wherein the risperidone base in particle form comprises particles having an average particle size ranging from 0.1 μm to 125 μm.
18. The method of claim 1 , wherein the risperidone base is released from the formulation for one week.
19. The method of claim 1 , wherein the risperidone base is released from the formulation for one month.
20. The method of claim 1 , wherein the risperidone base in particle form comprises particles having a particle size less than 38 μm.