Jet milling--a new technique for microparticle preparation.

An innovative technique for solvent free preparation of microparticles is described. Microparticles were prepared by a melt grinding technique which consists of three consecutive steps of melting in case of placebo microparticles or co-melting of polymer and drug in case of drug loaded microparticles, respectively, and pregrinding. In a final jet milling step the reduction of the particle size and smoothening of the microparticle surface occurred. Different polymers of PLA and PLGA type were utilised. The influence of the preparation parameters during the process were investigated according to microparticle properties like particle size distribution, habitus or surface morphology by executing a 2((5-2)) factorial design. The minimum mean particle size distribution (x(50) value) reached 4-6 microm. Scanning electron microscopy revealed that non-porous microparticles with a smooth surface were prepared. The release pattern of estrioltriacetate loaded microparticles of Resomer 202H nearly followed a zero order release kinetic over a period of 21 days without an initial burst effect. The preparation process can be carried out in a reproducible manner. The results demonstrate that microparticle preparation is possible by the following unique melt grinding technique without using organic solvents.