Granted Patent B2

US 8,293,871 · App. 11/578,712 · Granted Oct 23, 2012

Abstract

Claims (10)

1. A process of preparing a pharmaceutically acceptable composition in the form of microparticles for the sustained release of exendin-4 comprising:

a) forming a mixture by combining an aqueous phase comprising water soluble exendin-4 polypeptide and sucrose in the absence of ammonium sulfate with an oil phase comprising a purified 50:50 DL PLG 4A polymer in methylene chloride, wherein the purified polymer has an inherent viscosity of between about 0.3 and 0.5 dL/g;

b) forming a water-in-oil emulsion of the mixture from step a, wherein the inner emulsion droplet size is about 0.1 to 1.2 microns;

c) adding a coacervation agent to the mixture to form embryonic microparticles, wherein the coacervation agent is silicone oil added in an amount sufficient to achieve a silicone oil to polymer solvent ratio of from about 1:1 to about 1.5:1, and wherein the silicone oil is added to the water-in-oil emulsion in from about 3 minutes to about 5 minutes and the coacervation mixture is held for less than or about 1 minute;

d) transferring the embryonic microparticles to a quench solvent at a ratio of 16:1(v/v) quench solvent to methylene chloride to harden the embryonic microparticles to form hardened micro articles, wherein the quench solvent is a heptane/ethanol mixture and the transfer time is less than or about 3 minutes;

e) collecting the hardened microparticles; and

f) drying the hardened microparticles;

wherein the exendin-4 is resent at from about 3% w/w to about 5% w/w of the total weight of the composition; the composition has a C max to C ave ratio of about 3 or less; and the total pore volume of the composition is about 0.1 mL/g or less.

2. The process of claim 1 , wherein in step b, the inner emulsion droplet size is about 0.2 to 0.4 microns.

3. The process of claim 1 , wherein the exendin-4 is present at about 5% w/w of the total weight of the composition.

Assignments (12)