Drug stability and product performance characteristics of a dapivirine-releasing vaginal ring under simulated real-world conditions

Abstract

In two recent Phase III clinical trials, use of a 25 mg dapivirine vaginal ring significantly reduced HIV acquisition rates. Post hoc analysis from one of the trials indicated higher rates of protection among women over the age of 21 years when compared to younger women, most likely due to reduced adherence in the latter group. There is currently no information available on how release of dapivirine from the ring is affected by either its intermittent removal from the vagina or women's cleaning of the ring before re-insertion. Here, in vitro drug stability and product performance characteristics of the dapivirine ring were assessed under simulated conditions of real-world use. The impact of systematic deviations from the 28-day continuous use protocol upon in vitro release performance, was investigated. Also, the effect of ring exposure to a range of common household chemicals-including bath salts, bleach, detergent and personal lubricants-was examined through measurement of dapivirine content and stability. Dapivirine in vitro release under intermittent schedules was similar to that obtained under the normal continuous schedule ignoring the periods of interruption. Ring exposure to various household chemicals had no discernible impact on dapivirine assay value, degradation or stability.

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

“…Independent of the IVR design and the drug(s) to be delivered, IVRs are designed to provide controlled drug release over extended periods of time and should ensure a safe and effective drug therapy and a good patient adherence. However, women’s use of a ring may deviate from perfect use [95]. The IVR might, for instance, be intentionally removed or be expelled periodically.…”

“…The IVR might, for instance, be intentionally removed or be expelled periodically. Recently, Murphy et al presented results of an in vitro study targeted on simulating the imperfect use of a dapavirine-releasing IVR [95]. They addressed the impact of systematic deviations (removal and storage of the IVR for different time periods) from a 28-day continuous-use protocol upon release performance.…”

“…They addressed the impact of systematic deviations (removal and storage of the IVR for different time periods) from a 28-day continuous-use protocol upon release performance. Furthermore, they assessed the effect of ring exposure to a range of common household chemicals and cosmetics, that in real-life conditions might be used for IVR cleansing or vaginal hygiene, on drug load and stability [95]. Even though the in vitro release experiments performed in the cited study were performed in a typical shake-flask setup and thus, cannot necessarily be regarded as biorelevant, the human factors addressed in this study might also be a facet to be considered in biorelevant test designs.…”

Use of simulated vaginal and menstrual fluids to model in vivo discolouration of silicone elastomer vaginal rings

“…However, some women have voiced concerns regarding vaginal ring hygiene, particularly during menses ( van der Straten et al, 2016 ; Duby et al, 2020 ; Watnick et al, 2018 ). Surface discolouration of silicone elastomer vaginal rings during clinical use has been reported in the scientific literature ( Kiser et al, 2012 ; van der Straten et al, 2016 ; Kestelyn et al, 2018 ; Ballagh, 2001 ; Murphy et al, 2019a ; Das et al, 2015 ; Murphy et al, 2019b ). In the absence of confirmatory studies, it has been widely assumed that this discolouration is due to cervicovaginal fluid and/or menstrual blood; in truth, little is known about the causes of discolouration.…”

The Vaginal Microbiota, Bacterial Biofilms and Polymeric Drug-Releasing Vaginal Rings

“…A very small number of articles within the scientific literature have reported discoloration during use of VRs [208,[227][228][229]; in all likelihood, the phenomenon is significantly under-reported. For example, physical analysis of reservoir-type, silicone elastomer VRs containing either progesterone, d-norgestrel or norethindrone showed surface discoloration and brown staining following clinical use [227].…”