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

Abstract

The vagina is a promising site for both local and systemic drug delivery and represents an interesting administration route for compounds with poor oral bioavailability. Whereas most of the currently marketed dosage forms were designed as immediate release formulations, intravaginal rings (IVRs) offer the possibility of a controlled vaginal drug delivery over several weeks or months. For a long time, the development of IVRs was limited to steroid-releasing formulations. Recently, IVRs have witnessed a surge of new interest as promising delivery systems for microbicides. Therefore, various novel IVR designs have been introduced. To ensure that only safe and effective IVRs will be administered to patients, it is important to properly distinguish between IVRs with desired and undesired release performance. In vitro methods for evaluating drug release of IVRs that present with sufficient predictive capacity for in vivo drug release, and discriminatory power with regard to IVRs quality, are an essential tool for this purpose. The objective of the present review article is to present the current status of in vitro drug release testing of IVRs and to critically discuss current compendial and non-official in vitro drug release methods with regard to their discriminatory power and in vivo predictivity.

Multipurpose Prevention Technologies: Oral, Parenteral, and Vaginal Dosage Forms for Prevention of HIV/STIs and Unplanned Pregnancy

“…Thus, it is crucial to diligently assess DDIs to ensure each API within the formulation remains unaffected by other drugs and remains in its therapeutic window for the entire release duration. Additionally, IVRs are the most developed MPT formulation and hold the most potential to date; however, it is important to note that there is no universally accepted protocol in place for in vitro release studies, such as in vitro release media, media volume, pH, or drug release under agitation [ 145 ]. This makes comparisons between various IVR products and in vivo correlations challenging, which can result in many timely iterations in MPT IVR formulation development.…”

A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix

“…Since P70 is the formulation that released the greatest amount of DSF, this batch was chosen to compare the dissolution of DSF between SVF and 2% SDS aqueous solutions. Many studies, such as those of Boyd et al (2014) and Tiez et al (2019), have acquired in vitro drug release data for their disulfiram-loaded devices in a 2% SDS solution [7,44]. At this point the in vitro method was mainly designed for evaluation purposes, namely, to ensure a specific release pattern within a certain time frame and to discriminate between good and bad batches, rather than for simulating in vivo conditions.…”

In Vitro–In Vivo Correlation (IVIVC) Population Modeling for the In Silico Bioequivalence of a Long-Acting Release Formulation of Progesterone

“…Between the different types of vaginal drug delivery systems currently available on the market [ 21 , 22 , 23 , 24 ], intravaginal rings (IVRs) offer the possibility of a continuous and controlled drug release over an extended time period of several weeks. IVRs are generally used for the steroid administration in hormone replacement therapy or birth control, but more recently, they have witnessed a surge of new interest in the context of the HIV-prevention strategies [ 25 ]. Even with the increasing number of marketed products and the numerous IVR formulations that are currently in development, no regulatory guidance on the release tests or IVIVC assessment for vaginal rings are available in the United States, Europe, or Japan.…”