In vitro drug release, mechanical performance and stability testing of a custom silicone elastomer vaginal ring releasing dapivirine and levonorgestrel

Diarmaid J Murphy; Yahya H Dallal Bashi; Clare F McCoy; Peter Boyd; Leeanne Brown; François Martin; Nicole McMullen; Kyle Kleinbeck; Bindi Dangi; Patrick Spence; Bashir Hansraj; Bríd Devlin; R Karl Malcolm

doi:10.1016/j.ijpx.2022.100112

In vitro drug release, mechanical performance and stability testing of a custom silicone elastomer vaginal ring releasing dapivirine and levonorgestrel

Int J Pharm X. 2022 Jan 25:4:100112. doi: 10.1016/j.ijpx.2022.100112. eCollection 2022 Dec.

Affiliations

¹ School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
² Elkem Silicones, Two Tower Centre Boulevard, Suite 1802, East Brunswick, NJ 08816, USA.
³ International Partnership for Microbicides, Silver Spring, MD 2910, USA.

Abstract

We have previously reported a multipurpose silicone elastomer vaginal ring providing sustained release of dapivirine (an antiretroviral) and levonorgestrel (a progestin) for HIV prevention and hormonal contraception. During initial development, issues arose due to reaction between the ethynyl group in the levonorgestrel molecule and the hydride-functionalised polydimethylsiloxane components in the silicone elastomer formulation. This unwanted reaction occurred both during and to a lesser extent after ring manufacture, impacting the curing process, the mechanical properties of the ring, and the in vitro release of levonorgestrel. Recently, we reported custom silicone elastomer grades that minimise this reaction. In this follow-on study, we describe the manufacture, in vitro drug release, mechanical, and pharmaceutical stability testing of ring formulations prepared from a custom silicone elastomer and containing 200 mg dapivirine and 80, 160, 240 or 320 mg levonorgestrel. The rings showed mechanical properties similar to marketed ring products, sustained in vitro release of both drugs over 30 days in quantities deemed clinically relevant, offered acceptable assay values, and provided good product stability over 15 weeks at 40 °C and 75% relative humidity.

Keywords: HIV microbicide; Hormonal contraception; In vitro drug release; Mechanical properties; Multipurpose prevention technology (MPT); Silicone elastomer.