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

International Journal of Pharmaceutics: X

Matthew Kihara¹  François Martin¹  Nicole McMullen¹  Leeanne Brown¹  Patrick Spence²  Bashir Hansraj²  Kyle Kleinbeck²  Bindi Dangi²  Brid Devlin²  Clare F. McCoy³  R. Karl Malcolm³  Peter Boyd³  Yahya H. Dallal Bashi³  Diarmaid J. Murphy³ 

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

关键词: Vaginal rings;    HIV microbicide;    Multipurpose prevention technology (MPT);    Silicone elastomer;    Hormonal contraception;    Mechanical properties;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown