Preparation of microparticles having improved flowability

1. A method for processing microparticles to improve flowability, comprising:

(a) conditioning the microparticles to form conditioned microparticles, wherein the microparticles comprise an active agent selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts of the foregoing, a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing, wherein the conditioning is carried out by maintaining the microparticles at a conditioning temperature of about 25° C. for a period of at least about 5 days;

(b) measuring a flowability index of the conditioned microparticles; and

(c) if the flowability index of the conditioned microparticles is not greater than about 60, repeating step (a) until the flowability index of the conditioned microparticles is greater than about 60.

2. A method for preparing microparticles having improved flowability, comprising:

(a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises an active agent selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts of the foregoing, a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing, and a solvent for the polymer;

(b) extracting the solvent from the emulsion to form microparticles; and

(c) conditioning the microparticles to form conditioned microparticles, wherein the conditioning is carried out by maintaining the microparticles at a conditioning temperature of about 25° C. for a period of at least about 5 days;

(d) measuring a flowability index of the conditioned microparticles; and

(e) if the flowability index of the conditioned microparticles is not greater than about 60, then repeating step (c) until the flowability index of the conditioned microparticles is greater than about 60.

3. The method of claim 2 , wherein step (b) comprises:

(i) transferring the emulsion to a solvent extraction medium.

4. The method of claim 2 , wherein step (c) is carried out in a temperature-controlled chamber.

5. The method of claim 2 , wherein the solvent comprises benzyl alcohol and ethyl acetate.

6. A method for preparing microparticles having improved flowability, comprising:

(a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises an active agent selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts of the foregoing, a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing, and a solvent for the polymer;

(b) extracting the solvent from the emulsion to form microparticles; and

(c) hardening the microparticles to form hardened microparticles, wherein the hardening is carried out by maintaining the microparticles at a temperature of about 25° C. for a period of at least about 5 days;

(d) measuring a flowability index of the hardened microparticles; and

(e) if the flowability index of the hardened microparticles is not greater than about 60, then repeating step (c) until the flowability index of the hardened microparticles is greater than about 60.

7. The method of claim 6 , wherein step (c) is carried out until a hardness of the hardened microparticles is greater than about 0.4 MPa.

8. The method of claim 1 , wherein a hardness of the conditioned microparticles is greater than about 0.4 MPa.

9. The method of claim 2 , wherein a hardness of the conditioned microparticles is greater than about 0.4 MPa.

10. A method for processing microparticles to improve flowability, comprising:

(a) selecting a time period for processing the microparticles, wherein the time period is at least about 5 days, and wherein the microparticles comprise an active agent selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts of the foregoing, a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing;

(b) maintaining the microparticles at a conditioning temperature of about 25° C. for the time period;

(c) measuring a flowability index of the microparticles;

(d) if the flowability index of the microparticles is not greater than about 60, adjusting the conditioning temperature and the time period so that the flowability index of the microparticles is greater than about 60.

11. A method for processing microparticles to improve flowability, comprising:

(a) determining a time period for processing the microparticles, wherein the time period is at least about 5 days, and wherein the microparticles comprise an active agent selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts of the foregoing, a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing;

(b) maintaining the microparticles at a conditioning temperature of about 25° C. for the time period, wherein a flowability index of the microparticles at the completion of the maintaining step is greater than about 60.

12. The method of claim 11 , wherein the determining step comprises:

(i) measuring a flowability index of the microparticles;

(ii) if the flowability index of the microparticles is not greater than about 60, adjusting the conditioning temperature and the-time period so that the flowability index of the microparticles at the completion of the maintaining step is greater than about 60.