The polymer-alloys method as a new preparation method of biodegradable microspheres: Principle and application to cisplatin-loaded microspheres

The new preparation method for multi-reservoir type microspheres was investigated on the basis of the phase separation of poly(or-lactic acid) (PLA) and poly(DL-lactic-co-glycolic acid) (PLGA). Phase diagram study suggested that, in the PLA-PLGA-methylene chloride ternary system, the distinctive phase separation occurred when the total polymer concentration exceeded a critical level. The critical polymer concentration inducing this phase separation was found independent of the PLA/PLGA ratio but highly dependent on the solvent species, molecular weight, or lactide/glycolide ratio of PLGA. When various amino acid powders were added to the resultant biphasal polymeric solution, each powder was distributed either to the PLGA-rich phase or to the PLA-rich phase depending on its solubility parameter. It was also found that cisplatin powder was completely distributed in the PLGA-rich phase. Utilizing these findings, the preparation of the multi-reservoir type microspheres of cisplatin was tried. The PLGA-PLA biphasal polymeric solution dispersing the drug powder was emulsified, and then solidified by the solvent evaporation method. Microscopic observation proved that the obtained microspheres have the unique 'polymer alloys' structure and the drug was distributed in the internal phase (PLGA-rich phase). The encapsulation efficiency was almost 100% at 16% loading. The in vitro dissolution study revealed that the release of cisplatin lasted 45 days without initial burst. (C) 1997 Elsevier Science B.V.