In vitro and in vivo evaluation of thyrotrophin releasing hormone release from copoly(dl-lactic/glycolic acid) microspheres.

In vitro and in vivo release of thyrotrophin releasing hormone (TRH) from copoly(dl-lactic/glycolic acid) (PLGA) microspheres were evaluated. Factors affecting the TRH release from the microspheres were examined 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 than in neutral medium. The release rate of TRH from the PLGA microspheres increased with the increase in the degradation rate of PLGA. A decrease in an osmolarity of the medium also caused an increase in the TRH release rate even though no significant change in PLGA degradation was observed. The effect of osmolarity appears to be characteristic of water-soluble drug-containing microspheres composed of hydrophobic polymer. The release rate of TRH from PLGA microspheres was largely affected by the medium composition in the in vitro release test. A proper choice 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 following administration to rats correlated with the in vitro release in pH 7, 1/30 M buffer.