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.

Comparative Analysis of Lactobacillus gasseri and Lactobacillus crispatus Isolated From Human Urogenital and Gastrointestinal Tracts

“…A variety of organic acids such as lactic acid, acetic acid, succinic acid, and propionic acid, has been identified in the vaginal environment, with lactic acid being the major acid (Boskey et al, 2001). While some published studies investigating vaginal fluids focused on drug delivery and diffusion properties (Rastogi et al, 2016;Tietz and Klein, 2018), relatively few studies investigated bacterial growth (Juárez Tomás and Nader-Macías, 2007), and some do not account for the relevant acidic vaginal pH (Geshnizgani and Onderdonk, 1992;Owen and Katz, 1999). The SVF presented in this work has a pH of 4.5 and components that represent the actual vaginal fluid.…”

In vitro release testing methods for drug-releasing vaginal rings

“…Driven by efforts to provide better in vitro-in vivo correlations (IVIVCs; see later section) and physiological relevance for vaginally-administered products, there has been a move in recent years towards use of release media that more closely mimic the chemical composition, pH and volume of vaginal fluid [47,69]. Although its composition is affected by contributions from cervical mucus (pH ~8.0) [70], semen (pH ~7.5) [71] and menstrual material, normal vaginal fluid in pre-menopausal and post-menopausal women is generally within the pH range 4-5 and >5, respectively [47].…”

“…80 (also known as Polysorbate 80), Solutol HS15 (also known as Kolliphor HS15) and benzalkonium chloride(Table 1)[7,36,48,69,[91][92][93][94].…”

In Vitro Methods for Evaluating Drug Release of Vaginal Ring Formulations—A Critical Review

“…Biorelevant test conditions should properly address the in vivo situation, i.e., the volume and composition of vaginal fluid [85] and the temperature in the vaginal vault. Attention should also be paid to the need of simulating changes in the vaginal microenvironment during the menstrual cycle, ageing or due to sexual intercourse.…”