Details for Patent: 8,852,638

Title:	Sustained release small molecule drug formulation
Abstract:	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.sub.max to C.sub.min ratio less than 200 and lag time less than 0.2.
Inventor(s):	Luk; Andrew S. (Castro Valley, CA), Junnarkar; Gunjan H. (Palo Alto, CA), Chen; Guohua (Sunnyvale, CA)
Assignee:	Durect Corporation (Cupertino, CA)
Filing Date:	Sep 26, 2006
Application Number:	11/535,398
Claims:	1. An injectable depot formulation, comprising: a biocompatible polymer comprising a copolymer of lactic acid and glycolic acid, wherein the biocompatible polymer has a number average molecular weight ranging from 1000 Daltons to 5000 Daltons; an organic solvent combined with the biocompatible polymer to form a viscous gel said solvent selected from the group consisting of benzyl alcohol, benzyl benzoate, ethyl benzoate, ethyl hydroxide, N-methy1-2-pyrrolidone, and mixtures thereof; and a small molecule drug selected from base and salt forms of risperidone incorporated in the viscous gel, wherein the small molecule drug is in the form of particles having a particle size less than 38 .mu.m, wherein the salt forms of risperidone have less than 1 mg/mL solubility in water, and wherein the formulation exhibits an in vivo release profile having C.sub.max to C.sub.min ratio less than 200 over a period of one month. 2. The formulation of claim 1, wherein the in vivo release profile has C.sub.max to C.sub.min ratio less than 30. 3. The formulation of claim 1, wherein the solvent has a miscibility in water less than 7 % by weight. 4. A method of administering a small molecule drug to a subject in a controlled manner, said method comprising implanting in the subject an effective amount of an injectable depot formulation comprising: a biocompatible polymer comprising a copolymer of lactic acid and glycolic acid, wherein the biocompatible polymer has a number average molecular weight ranging from 1000 Daltons to 5000 Daltons; an organic solvent combined with the biocompatible polymer to form a viscous gel, said solvent selected from the group consisting of benzyl alcohol, benzyl benzoate, ethyl benzoate, ethyl hydroxide, N-methy1-2-pyrrolidone, and mixtures thereof; and a small molecule drug selected from base and salt forms of risperidone incorporated in the viscous gel, wherein the small molecule drug is in the form of particles having a particle size less than 38 .mu.m, wherein the salt forms of risperidone have less than 1 mg/mL solubility in water, and wherein the formulation exhibits an in vivo release profile having C. to C.sub.min ratio less than 200 over a period of one month. 5. The formulation of claim 1, wherein the formulation exhibits a lag time less than 0.2. 6. The formulation of claim 1, wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 60:40 to 75:25. 7. The formulation of claim 1, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the biocompatible polymer is present in the depot gel vehicle in an amount ranging from 5 wt % to 40 wt %. 8. The formulation of claim 1, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the organic solvent is present in the depot gel vehicle in an amount ranging from 20 wt % to 40 wt %. 9. The formulation of claim 1, wherein the small molecule drug is present in the formulation in an amount ranging from 5 wt % to 40 wt %. 10. The method of claim 4, wherein the formulation exhibits a lag time less than 0.2. 11. The method of claim 4, wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 60:40 to 75:25. 12. The method of claim 4, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the biocompatible polymer is present in the depot gel vehicle in an amount ranging from 5 wt % to 40 wt %. 13. The method of claim 4, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the organic solvent is present in the depot gel vehicle in an amount ranging from 20 wt % to 40 wt %. 14. The method of claim 4, wherein the small molecule drug is present in the formulation in an amount ranging from 5 wt% to 40 wt%. 15. The formulation of claim 1, wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 50:50 to 100:0. 16. The formulation of claim 1, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the biocompatible polymer is present in the depot gel vehicle in an amount ranging from 5 wt % to 60 wt %. 17. The formulation of claim 1, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the organic solvent is present in the depot gel vehicle in an amount ranging from 20 wt % to 60 wt %. 18. The method of claim 4, wherein the copolymer of lactic acid and glycolic acid has a monomer ratio of lactic acid to glycolic acid ranging from 50:50 to 100:0. 19. The method of claim 4, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the biocompatible polymer is present in the depot gel vehicle in an amount ranging from 5 wt % to 60 wt %. 20. The method of claim 4, wherein the biocompatible polymer and the organic solvent comprise a depot gel vehicle, and wherein the organic solvent is present in the depot gel vehicle in an amount ranging from 20 wt% to 60 wt %.