In Vitro Characterization of Six Month Dosage Forms for a GnRH Antagonist

Autor: Jabar A. Faraj, Patrick P. DeLuca, Santos B. Murty, Susan D’Souza
Rok vydání: 2014
Předmět:
Zdroj: Advances in Pharmaceutics. 2014:1-10
ISSN: 2314-775X
2356-6841
Popis: The objective of this study was to develop long-acting injectable dosage forms of Orntide, a peptide GnRH antagonist, to provide tailored release for 6-month duration. Using a polylactide homopolymer and the solvent extraction/evaporation method, three microsphere formulations (Formulations A, B, and C) were prepared at various drug loadings (11.85–15.79%). The microspheres were characterized for particle size by laser diffractometry, surface morphology by scanning electron microscopy (SEM), and bulk density by tapping, as well as long-term in vitro drug release, mass loss and hydration at 37°C, and short-term in vitro drug release at elevated temperatures (51–59°C). Experiments at 37°C revealed that drug release was triphasic and occurred due to slow degradation of the polylactide polymer. Short-term in vitro release results indicated that drug release was diffusional. Application of the Higuchi equation to short-term release confirmed the temperature dependency of the diffusional rate constant. Using the rate constant and the Arrhenius equation, an value of 45 kcal/mol (Formulation A) and approximately 25 kcal/mol (Formulations B and C) was obtained for diffusional release. Study results suggest that by selection of an appropriate biodegradable polymer, injectable dosing forms that release drug for 6 months or longer can be developed.
Databáze: OpenAIRE
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