Table of Contents
Advances in Pharmaceutics
Volume 2014 (2014), Article ID 435963, 10 pages
http://dx.doi.org/10.1155/2014/435963
Research Article

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

1Sunovion Pharmaceuticals Inc., Marlborough, MA 01752, USA
2Murty Pharmaceuticals, 518 Codell Drive, Lexington, KY 40509, USA
3Evonik, 750 Lakeshore Parkway, Birmingham, AL 35211, USA
4University of Kentucky College of Pharmacy, Lexington, KY 40536, USA

Received 4 April 2014; Accepted 28 May 2014; Published 15 July 2014

Academic Editor: Maria Cristina Bonferoni

Copyright © 2014 Susan D’Souza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.