Design and Development of an in Vitro Assay for Evaluation of Solid Vaginal Dosage Forms

Vaginal dosage forms are seen as a viable option for empowering women to protect themselves from the risk of HIV transmission. Because of limited research in the field, there is a lack of suitable dissolution methods established for determination of drug release from vaginal formulations inside the vaginal tract. The main aim of this study was to develop a simple, reliable and reproducible in vitro release method for evaluation of solid vaginal dosage forms (VDFs) which was hoped to exhibit a close in vitro-in vivo correlation. Dapivirine, a drug being developed as a microbicide and a well established marketed anti fungal drug, Clotrimazole were used as model drugs. Two doses (0.5 mg and 1.25 mg) of Dapivirine were prepared as novel rapidly disintegrating, bioadhesive tablets. Clotrimazole 100 mg, prepared in house as conventional release tablets and commercially available Canesten (Clotrimazole tablet 100 mg) were used. The in vitro drug release testing of these tablets was carried out using a designed system which consisted of modified USP dissolution Apparatus II in conjunction with Enhancer cell (as sample holder) in 150 ml capacity flasks instead of the standard 900 ml flasks. The suitability of the system was investigated for variable parameters such as formulation types, drug concentration, stirring speeds, media volume and comparison of in house product with marketed product. The method was successfully optimized at a volume of 100 ml and a low speed of 25 rpm at pH 4 and was found sensitive enough to distinguish between formulations and evaluate products of different strengths. A linear drug release profile (R = 0.99) was obtained in case of Dapivirine, indicating that drug release is controlled by diffusion. The developed dissolution system has a potential to exhibit a good in vitro-in vivo correlation in addition to carrying out routine dissolution tests for solid VDFs.