Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology

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• 作者：Christopher McConville^a ; ^{C.McConville.2@bham.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Ian Major^b ; Brid Devlin^c ; Andrew Brimer^c
• 关键词：Multipurpose prevention technology ; HIV microbicides ; Contraception ; Sexually transmitted infections ; Dapivirine ; Levonorgestrel ; Acyclovir
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：104
• 期：Complete
• 页码：171-179
• 全文大小：532 K

文摘

Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8 h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8 h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153 N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control.