Development Of In Vitro-In Vivo Correlation In Controlled-Release Etonogestrel Microspheres

By Akihisa Nonoyama, Ph.D., David R. Friend, Ph.D., Cory Berkland, Ph.D., and Nathan Dormer, Ph.D., Adare Pharma Solutions

A significant duration gap exists between three months and three years in FDA-approved long-acting contraceptives (LACs). To address this unmet clinical need, a microsphere formulation of etonogestrel encapsulated in a biodegradable polylactic acid (PLA) polymer was developed. This formulation aims to provide sustained release of the contraceptive over a six to twelve-month period.

Stratµm™ technology, employed by Adare Pharma Solutions, enabled the fabrication of monodisperse microspheres with an average diameter of approximately 30 micrometers. In vitro release studies demonstrated the controlled release profile of etonogestrel from these microspheres. Furthermore, in vivo evaluation in female Sprague-Dawley rats confirmed a sustained release period of nine months. A Fickian diffusion model accurately described the in vitro release kinetics, facilitating the establishment of an in vitro-in vivo correlation (IVIVC).

The monodisperse nature of the microspheres, achieved through Stratµm technology, offers advantages in terms of CMC as well as injectability. Review a proof-of-concept for a microsphere-based etonogestrel formulation capable of delivering sustained contraceptive effects for nine months. The generated IVIVC provides a valuable tool for optimizing future iterations of this formulation.