Preparation of Three-Month Depot Injectable Microspheres of Leuprorelin Acetate Using Biodegradable Polymers
- 1 January 1994
- journal article
- Published by Springer Science and Business Media LLC in Pharmaceutical Research
- Vol. 11 (8), 1143-1147
- https://doi.org/10.1023/a:1018936815654
Abstract
To obtain a three-month release injection of leuprorelin acetate, microspheres were prepared with copoly(DL-lactic/glycolic acid) or poly(DL-lactic acid) (PLA) using an in-water drying method, and drug release was evaluated. The content of water-soluble oligomers in the polymers was found to strongly affect the initial burst, and reducing the content to less than 0.1% was necessary to keep the first-day release below 10%. Drug loading of more than 15% also increased the initial drug release; the acceptable maximum loading was 12%. Elevation of the glass transition temperature of the microspheres was observed with an increase in drug loading. This suggests formation of a rigid structure, possibly with arrangement of the polymer around the drug cores like in a micelle. This structure provides a hydrophobic barrier against diffusion of the hydrophilic peptide, resulting in high trapping efficiency and long-term sustained release dependent on polymer erosion. The microspheres prepared with PLA having a m.w. of 12,000 to 18,000 provided linear sustained release and persistent serum levels of the drug in rats for over 3 months.Keywords
This publication has 13 references indexed in Scilit:
- Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind studyFertility and Sterility, 1990
- Clinical Study of Leuprolide Depot Formulation in the Treatment of Advanced Prostate CancerJournal of Urology, 1990
- Controlled Release of LHRH Agonist, Leuprolide Acetate, from Microcapsules: Serum Drug Level Profiles and Pharmacological Effects in AnimalsJournal of Pharmacy and Pharmacology, 1989
- A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomataFertility and Sterility, 1989
- One-month release injectable microcapsules of a luteinizing hormone-releasing hormone agonist (leuprolide acetate) for treating experimental endometriosis in rats.1988
- In vivo release profiles of leuprolide acetate from microcapsules prepared with polylactic acids or copoly(lactic/glycolic) acids and in vivo degradation of these polymers.CHEMICAL & PHARMACEUTICAL BULLETIN, 1988
- A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid.CHEMICAL & PHARMACEUTICAL BULLETIN, 1988
- Tissue Response to Biodegradable Injectable MicrocapsulesJournal of Biomaterials Applications, 1987
- Preparation and in vitro degradation properties of polylactide microcapsules.CHEMICAL & PHARMACEUTICAL BULLETIN, 1985
- Long-acting delivery systems for narcotic antagonists. 1Journal of Medicinal Chemistry, 1973