Simulated genital tract fluids and their applicability in drug release/dissolution testing of vaginal dosage forms

Abstract

There has been a trend towards the development of novel vaginal dosage forms both for local therapy and systemic absorption. The growing number of vaginal dosage forms, however, presents with an increasing demand for appropriate in vitro test methods for ensuring a safe and reliable in vivo performance of each of the formulations. Application of biorelevant in vitro parameters, i.e., addressing in vivo parameters that significantly affect drug release from a vaginal dosage form in an in vitro test setup, could ensure that the results of the dissolution/drug release test are clinically meaningful and also predictive for detection of changes in the post-approval drug product. Thus, the development of predictive in vitro test methods for vaginal dosage forms is of great interest. A number of simulated vaginal fluids have been introduced in the recent past. In addition, several other genital fluids that could affect the intravaginal fluid composition, such as simulated cervical fluid/mucus, simulated intrauterine fluid, and simulated semen have been described in the literature. More frequent use of these media can be assumed, and future experiments will show if the current media will require more fine-tuning to even better reflect all physiological parameters that can affect drug release/dissolution in the vagina or if there is also a chance to simplify these media without losing their biorelevance.