Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel

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

doi:10.1016/j.ijpx.2021.100091

Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel

Int J Pharm X. 2021 Jul 14:3:100091. doi: 10.1016/j.ijpx.2021.100091. eCollection 2021 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

A dapivirine-releasing silicone elastomer vaginal ring for reducing women's risk of HIV acquisition has recently been approved. A next-generation multipurpose vaginal ring releasing dapivirine and levonorgestrel is currently in development, offering hormonal contraception and HIV prevention from a single device. Previously, we reported challenges with incorporating levonorgestrel into rings manufactured from addition-cure silicone elastomers due to an irreversible chemical reaction between the levonorgestrel molecule and the hydride-functionalised crosslinker component of the silicone elastomer formulation, leading to low drug content assay, cure inhibition, and reduced ring mechanical properties (which may account for the increased incidence of ring expulsion in vivo). Here, we report on the development and testing of various custom silicone elastomer materials specifically formulated to circumvent these issues. After extensive testing of the custom silicones and subsequent manufacture and testing (Shore M hardness, pot life, content assay, oscillatory rheology, mechanical testing) of rings containing both dapivirine and levonorgestrel, a lead candidate formulation was selected that was amenable to practical ring manufacture via injection molding, exhibited no substantial levonorgestrel binding, and offered suitable mechanical properties.

Keywords: HIV microbicide; Hormonal contraception; Mechanical properties; Multipurpose prevention technology (MPT); Rheology; Silicone elastomer; Vaginal rings.