Details for Patent: 9,044,450

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:	Mar 08, 2013
Application Number:	13/790,930
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, the organic solvent being selected from benzyl alcohol, benzyl benzoate, ethyl benzoate, ethyl hydroxide, N-methyl-2-pyrrolidone, and mixtures thereof; and a drug selected from base and salt forms of risperidone in particle form incorporated in the viscous gel, wherein the particles have a particle size less than 38 .mu.m, and wherein the salt forms of risperidone have less than 1 mg/mL solubility in water. 2. The formulation of claim 1, wherein the formulation exhibits an in vivo release profile having a 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 drug to a subject in a controlled manner, 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, the organic solvent being selected from benzyl alcohol, benzyl benzoate, ethyl benzoate, ethyl hydroxide, N-methyl-2-pyrrolidone, and mixtures thereof, and a drug selected from base and salt forms of risperidone in particle form incorporated in the viscous gel, wherein the particles have a particle size less than 38 .mu.m, and wherein the salt forms of risperidone have less than 1 mg/mL solubility in water. 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 vehicle, and wherein the biocompatible polymer is present in the 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 vehicle, and wherein the organic solvent is present in the vehicle in an amount ranging from 20 wt % to 40 wt %. 9. The formulation of claim 1, wherein the 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 vehicle, and wherein the biocompatible polymer is present in the 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 vehicle, and wherein the organic solvent is present in the vehicle in an amount ranging from 20 wt % to 40 wt %. 14. The method of claim 4, wherein the 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 vehicle, and wherein the biocompatible polymer is present in the 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 vehicle, and wherein the organic solvent is present in the 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 vehicle, and wherein the biocompatible polymer is present in the 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 vehicle, and wherein the organic solvent is present in the vehicle in an amount ranging from 20 wt % to 60 wt %. 21. The formulation of claim 1, wherein the biocompatible polymer and the organic solvent comprise a vehicle, the biocompatible polymer is present in the vehicle in an amount ranging from 5 wt % to 60 wt %, the organic solvent is present in the vehicle in an amount ranging from 20 wt % to 60 wt %, and the drug is present in the formulation in an amount ranging from 5 wt % to 40 wt %. 22. The method of claim 4, wherein the biocompatible polymer and the organic solvent comprise a vehicle, the biocompatible polymer is present in the vehicle in an amount ranging from 5 wt % to 60 wt %, the organic solvent is present in the vehicle in an amount ranging from 20 wt % to 60 wt %, and the drug is present in the formulation in an amount ranging from 5 wt % to 40 wt %.