IN-VITRO AND IN-VIVO EVALUATION OF THYROTROPIN-RELEASING-HORMONE RELEASE FROM COPOLY(DL-LACTIC GLYCOLIC ACID) MICROSPHERES/

In vitro and in vivo release of thyrotrophin releasing hormone (TRH) f rom copoly(dl-lactic/glycolic acid) (PLGA) microspheres were evaluated . Factors affecting the TRH release from the microspheres were examine d to clarify the release mechanisms by changing the medium composition in the in vitro release test. The hydrolysis rate of PLGA, the matrix -forming substance in the microspheres, was faster in acidic medium th an in neutral medium. The release rate of TRH from the PLGA microspher es increased with the increase in the degradation rate of PLGA. A decr ease in an osmolarity of the medium also caused an increase in the TRH release rate even though no significant change in PLGA degradation wa s observed. The effect of osmolarity appears to be characteristic of w ater-soluble drug-containing microspheres composed of hydrophobic poly mer. The release rate of TRH from PLGA microspheres was largely affect ed by the medium composition in the in vitro release test. A proper ch oice of medium was found to be important for the estimation of in vivo release. The in vivo release rate of TRH from the PLGA microspheres f ollowing administration to rats correlated with the in vitro release i n pH 7, 1/30 M buffer.