Process for preparing microparticles

摘要

A process for preparing microparticles comprising a biologically active material and a polymer and having a mean particle size expressed as the volume mean diameter (VMD) of from 10 to 500 μm, wherein the biologically active material is substantially insoluble in the polymer, which process comprises: a. contacting a mixture of the biologically active material or a precursor thereof, the polymer or a precursor thereof and a processing aid with a supercritical fluid which is capable of swelling the polymer under temperature and pressure conditions necessary to maintain the fluid in a supercritical state; b. allowing the supercritical fluid to penetrate and liquefy the polymer, while maintaining the temperature and pressure conditions so that the fluid is maintained in a supercritical state; c. releasing the pressure to precipitate microparticles comprising the biologically active agent and the polymer.

主权项

1. A process for preparing microparticles comprising a biologically active material and a polymer, wherein the microparticles have a mean particle size expressed as the volume mean diameter (VMD) of from 10 to 500 μm, wherein the biologically active material is insoluble in the polymer, and wherein the process comprises the following sequential steps:
a) contacting a mixture of the biologically active material, the polymer, and a processing aid with supercritical carbon dioxide, wherein the processing aid is selected from the group consisting of:
(i) fatty acids, sorbitan monooleate, polyoxyethylene (20) sorbitan monooleate, fatty acid esters consisting of polyglycol mono- and di-esters of 12-hydroxystearic acid and of about 30% free polyethylene glycol;(ii) 2-pyrrolidone, N-methyl-2-pyrrolidone, polymers of pyrrolidones;(iii) polypropylene glycol;(iv) medium chain mono-, di-, and tri-glycerides having a formula (CH2OR1)(CH2OR2)(CH2OR3) wherein R1, R2, and R3 are independently H or —C(O)(CH2)nCH3, wherein n is an integer from 6 to 8, provided that not all R1, R2, and R3 are H; and(v) poloxamers having a general formula HO(C2H4O)a(C3H6O)b(C2H4O)aH, wherein a is an integer from 2 to 130 and b is an integer from 15 to 67; b) allowing the supercritical carbon dioxide to penetrate and liquefy the polymer, whilst maintaining the temperature and pressure conditions so that the carbon dioxide is maintained in a supercritical state, and blending or mixing the supercritical carbon dioxide and liquefied polymer in a mixing chamber to form a blended mixture; c) removing the blended mixture from the mixing chamber into a separate container that is not under supercritical conditions through a nozzle or orifice, thereby forming the microparticles.