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) containing copoly(dl-lactic/glycolic acid) (PLGA) microspheres were evaluated 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. The drug release from the PLGA microspheres in vitro correlated well with that in vivo, and pseudo-zero-order release kinetics were observed. The pharmacokinetics of TRH following administration of this controlled-release parenteral dosage form have been also examined in rats. Following a transient increase in the plasma level due to an initial burst, steady-state plasma levels were observed. The duration of drug release estimated from the plasma level was comparable with the results in the in vitro and in vivo release studies. The steady-state plasma levels 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 reported in vivo sustained release of TRH achieved with this drug-delivery system.