Controlled Release of Thyrotropin Releasing Hormone from Microspheres: Evaluation of Release Profiles and Pharmacokinetics after Subcutaneous Administration

• Published in: Journal of pharmaceutical sciences 1994-06, Vol.83 (6), p.798-801
• Main Authors: Heya, Toshiro, Toguchi, Hajime, Mikura, Yasushi, Nagai, Akihiro, Miura, Yasutomo, Futo, Tomomichi, Tomida, Yoshinao, Shimizu, Hisayoshi
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Hormones. Endocrine system; Injections, Subcutaneous; Lactic Acid; Male; Medical sciences; Microspheres; Pharmacology. Drug treatments; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers - administration & dosage; Rats; Rats, Wistar; Thyrotropin-Releasing Hormone - administration & dosage; Thyrotropin-Releasing Hormone - pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600830608

The drug‐release kinetics of thyrotropin releasing hormone (TRH) containing copoly(dl‐lactic/glycolic acid) (PLGA) microspheres were evaluated bothin vitroandin 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 microspheresin vitrocorrelated well with thatin 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 thein vitroandin vivorelease 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 reportedin vivosustained release of TRH achieved with this drug‐delivery system.