A NEW METHOD FOR THE PREPARATION OF DRUG CONTAINING POLYLACTIC ACID MICROPARTICLES WITHOUT USING ORGANIC-SOLVENTS

Microparticles of D,L-polylactic acid (PLA) prepared by a new method (melting method) were compared with microparticles obtained by the solvent evaporation/extraction method. For particle preparation by the melting method, the matrix polymer (D,L-PLA, MW 2000 or 16000) was melted in presence of the drug vinpocetine, a new neurotropic agent, to obtain a homogeneous mixture. After emulsification of the melt in a hot aqueous solution, microparticles were isolated by either pouring the hot emulsion into ice-water or spray drying. electron microscopy revealed a smooth surface of the D,L-PLA 2000 particles isolated by spray drying, whereas D,L-PLA 16000 microparticles and D,L-PLA 2000 isolated by centrifugation showed a rough surface. The mean diameter ranged from 2 to 22-mu-m, depending on the MW of the polymer and the isolation method. A faster drug release could be achieved by increasing the drug content or by addition of polyethylene glycol to D,L-PLA. These two factors are useful for influencing the release characteristics. For oral application an ideal retardation could be achieved with D,L-PLA 2000, whereas D,L-PLA 16000 microparticles showed a prolonged release characteristic over some days and should therefore be useful for intramuscular and subcutaneous administration. During the preparation of microparticles by melting, the MW was reduced by ca. 12%, as ascertained by end group titration. HPLC analysis demonstrated that the drug was stable during the preparation process.