CONTROLLED-RELEASE OF THYROTROPIN-RELEASING-HORMONE FROM MICROSPHERES- EVALUATION OF RELEASE PROFILES AND PHARMACOKINETICS AFTER SUBCUTANEOUS ADMINISTRATION
T. Heya et al., CONTROLLED-RELEASE OF THYROTROPIN-RELEASING-HORMONE FROM MICROSPHERES- EVALUATION OF RELEASE PROFILES AND PHARMACOKINETICS AFTER SUBCUTANEOUS ADMINISTRATION, Journal of pharmaceutical sciences, 83(6), 1994, pp. 798-801
The drug-release kinetics of thyrotropin releasing hormone (TRH) conta
ining copoly(dl-lactic/glycolic acid) (PLGA) microspheres were evaluat
ed both in vitro and in vivo. The drug was encapsulated in PLGA using
an in-water drying method through a water in oil in water emulsion. Th
e drug release from the PLGA microspheres in vitro correlated well wit
h that in vivo, and pseudo-zero-order release kinetics were observed.
The pharmacokinetics of TRH following administration of this controlle
d-release parenteral dosage form have been also examined in rats. Foll
owing a transient increase in the plasma level due to an initial burst
, steady-state plasma levels were observed. The duration of drug relea
se estimated from the plasma level was comparable with the results in
the in vitro and in vivo release studies. The steady-state plasma leve
ls correlated well with the levels predicted from the pharmacokinetic
parameters following a single subcutaneous or intravenous injection of
TRH solution. The results of this study confirm the previously report
ed in vivo sustained release of TRH achieved with this drug-delivery s
ystem.