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

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 fro...

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Autores principales: Dallal Bashi, Yahya H., Murphy, Diarmaid J., McCoy, Clare F., Boyd, Peter, Brown, Leeanne, Kihara, Matthew, Martin, François, McMullen, Nicole, Kleinbeck, Kyle, Dangi, Bindi, Spence, Patrick, Hansraj, Bashir, Devlin, Brid, Malcolm, R. Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683669/
https://www.ncbi.nlm.nih.gov/pubmed/34977558
http://dx.doi.org/10.1016/j.ijpx.2021.100091
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author Dallal Bashi, Yahya H.
Murphy, Diarmaid J.
McCoy, Clare F.
Boyd, Peter
Brown, Leeanne
Kihara, Matthew
Martin, François
McMullen, Nicole
Kleinbeck, Kyle
Dangi, Bindi
Spence, Patrick
Hansraj, Bashir
Devlin, Brid
Malcolm, R. Karl
author_facet Dallal Bashi, Yahya H.
Murphy, Diarmaid J.
McCoy, Clare F.
Boyd, Peter
Brown, Leeanne
Kihara, Matthew
Martin, François
McMullen, Nicole
Kleinbeck, Kyle
Dangi, Bindi
Spence, Patrick
Hansraj, Bashir
Devlin, Brid
Malcolm, R. Karl
author_sort Dallal Bashi, Yahya H.
collection PubMed
description 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.
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spelling pubmed-86836692021-12-30 Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel Dallal Bashi, Yahya H. Murphy, Diarmaid J. McCoy, Clare F. Boyd, Peter Brown, Leeanne Kihara, Matthew Martin, François McMullen, Nicole Kleinbeck, Kyle Dangi, Bindi Spence, Patrick Hansraj, Bashir Devlin, Brid Malcolm, R. Karl Int J Pharm X Research Paper 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. Elsevier 2021-07-14 /pmc/articles/PMC8683669/ /pubmed/34977558 http://dx.doi.org/10.1016/j.ijpx.2021.100091 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Dallal Bashi, Yahya H.
Murphy, Diarmaid J.
McCoy, Clare F.
Boyd, Peter
Brown, Leeanne
Kihara, Matthew
Martin, François
McMullen, Nicole
Kleinbeck, Kyle
Dangi, Bindi
Spence, Patrick
Hansraj, Bashir
Devlin, Brid
Malcolm, R. Karl
Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
title Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
title_full Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
title_fullStr Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
title_full_unstemmed Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
title_short Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
title_sort silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683669/
https://www.ncbi.nlm.nih.gov/pubmed/34977558
http://dx.doi.org/10.1016/j.ijpx.2021.100091
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