Development of a multi-layered vaginal tablet containing Dapivirine, Levonorgestrel and Acyclovir for use as a multipurpose prevention technology.

Abstract

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 multilayered 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 Dapivirnie for up to 8 hours. 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 hours. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs were between 115 and 153 Newtons, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at level 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison to a mixed drug control.