PHARMACEUTICAL DOSAGE FORM DESIGN OF COPO LY (LACTIC GLYCOLIC ACID) MICROSPHERES - MECHANISM OF IN-VITRO RELEASE OF GENTAMICIN/

The sustained release mechanism of gentamicin (GM) from lactic acid/gl ycolic acid copolymer (PLGA) microspheres was investigated. The termin al free carboxyl group of polymer was proved to be necessary for GM to be highly incorporated into microspheres by comparing interactions wi th GM and two types of polymers; free (ionized and non ionized) and th e terminal esterified carboxyl group of polymer. The weight-average mo lecular weights (Mws) of component PLGAs of microspheres with an ioniz able carboxyl group used here were approximately 4900 and 10000. The r elease pattern of GM was tested in phosphate buffered saline. The rele ase rate of GM was dependent on the initial Mw and surface form. The G M release continued for 20 and 30 d from PLGA 4900- and PLGA10000-micr ospheres, respectively. The changes of total weight of microspheres te nded to decrease with time, and the molecular weight distribution of P LGA gradually shifted to lower distribution, indicating a decrease in Mw. The changes and the shifts were dependent on the initial Mws of PL GAs but independent of their surface form. The half-times of wight los s of PLGA 4900- and PLGA10000-microspheres were about 10 and 20 d, res pectively. From these results, the release profile of GM from PLGA mic rospheres was explained by the following three steps, i.e., 1) the rel ease from the surface, 2) the relatively slow release caused by the ob struction of channels followed by the degradation of PLGA, 3) the rele ase accompanied by the erosion of microspheres.