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 i nvestigated on the basis of the phase separation of poly(or-lactic aci d) (PLA) and poly(DL-lactic-co-glycolic acid) (PLGA). Phase diagram st udy suggested that, in the PLA-PLGA-methylene chloride ternary system, the distinctive phase separation occurred when the total polymer conc entration exceeded a critical level. The critical polymer concentratio n 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 we re added to the resultant biphasal polymeric solution, each powder was distributed either to the PLGA-rich phase or to the PLA-rich phase de pending on its solubility parameter. It was also found that cisplatin powder was completely distributed in the PLGA-rich phase. Utilizing th ese findings, the preparation of the multi-reservoir type microspheres of cisplatin was tried. The PLGA-PLA biphasal polymeric solution disp ersing the drug powder was emulsified, and then solidified by the solv ent evaporation method. Microscopic observation proved that the obtain ed microspheres have the unique 'polymer alloys' structure and the dru g was distributed in the internal phase (PLGA-rich phase). The encapsu lation efficiency was almost 100% at 16% loading. The in vitro dissolu tion study revealed that the release of cisplatin lasted 45 days witho ut initial burst. (C) 1997 Elsevier Science B.V.