Sustained release of human growth hormone from microcapsules prepared by a solvent evaporation technique

• Published in: Journal of controlled release Vol. 88; no. 2; pp. 229 - 242
• Main Authors: Takada, Shigeyuki, Yamagata, Yutaka, Misaki, Masafumi, Taira, Keiko, Kurokawa, Tomofumi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07-03-2003; Elsevier
• Subjects: Acetates - chemistry; Ammonium acetate; Animals; Biological and medical sciences; Capsules; Copoly(dl-lactic/glycolic)acid (PLGA) microcapsules; Delayed-Action Preparations; Drug Compounding - methods; Emulsions; Freeze Drying; General pharmacology; Growth Hormone - administration & dosage; Growth Hormone - pharmacokinetics; Hormones. Endocrine system; Humans; Injections, Subcutaneous; Lyophilized protein microparticles; Male; Medical sciences; Microscopy, Electron, Scanning; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders; Rats; Rats, Sprague-Dawley; Recombinant human growth hormone (rhGH); Solvents; Sustained release; Zinc - administration & dosage; Zinc - pharmacokinetics; Sustained release; Ammonium acetate; Recombinant human growth hormone (rhGH); Copoly(dl-lactic/glycolic)acid (PLGA) microcapsules; Lyophilized protein microparticles; Encapsulation; Rat; Somatotropin hormone; Drug carrier; Zinc Oxides; Protein hormone; Anhydride copolymer; Subcutaneous administration; Release; Glycolic acid copolymer; Pharmaceutical technology; Controlled release form; Control release polymer; Rodentia; Microcapsule; Anhydride polymer; In vitro; In vivo; Vertebrata; Ester copolymer; Lactic acid polymer; Copoly(DL-lactic/glycolic)acid (PLGA) microcapsules; Mammalia; Adenohypophyseal hormone; Animal; Dosage form; Active ingredient
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(02)00494-7

Biodegradable microcapsules for sustained release of recombinant human growth hormone (rhGH) were prepared by a solid-in-oil-in-water (S/O/W) emulsion solvent evaporation technique using lyophilized protein microparticles. The minimum mean particle size of rhGH in S/O dispersions was 2.8–3.0 μm when ammonium acetate was added at molar ratios of 10–20 times against rhGH. High entrapment of rhGH in microcapsules was achieved by incorporating rhGH powder with a smaller particle size obtained by lyophilizing with ammonium acetate. As the particle size of rhGH decreased, the in vivo initial release decreased, while subsequent serum levels of rhGH in sustained release phase were higher. Addition of zinc oxide to microcapsules resulted in higher serum levels than those prepared without zinc oxide, suggesting a stabilizing effect of zinc oxide after subcutaneous injection into rats. The release profile of rhGH from microcapsules was controllable by selecting the proper copoly(dl-lactic/glycolic)acid (PLGA) with L/G ratio and molecular weight. Utilization of rhGH powder with a smaller particle size obtained by lyophilizing with ammonium acetate is essential for preparation of microcapsules with high entrapment and well-controlled sustained release profile with small initial release.