CONTROLLED-RELEASE OF THYROTROPIN-RELEASING-HORMONE FROM MICROSPHERES- EVALUATION OF RELEASE PROFILES AND PHARMACOKINETICS AFTER SUBCUTANEOUS ADMINISTRATION

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.