T. Heya et al., IN-VITRO AND IN-VIVO EVALUATION OF THYROTROPIN-RELEASING-HORMONE RELEASE FROM COPOLY(DL-LACTIC GLYCOLIC ACID) MICROSPHERES/, Journal of pharmaceutical sciences, 83(5), 1994, pp. 636-640
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.