The ins and outs of drug-releasing vaginal rings: a literature review of expulsions and removals

Abstract

1. Introduction 2. Factors potentially affecting ring expulsion 2.1. Dimensions of the human vagina 2.2. Ring dimensions 2.3. Types and grades of polymeric materials used to manufacture vaginal rings Silicone elastomers Ethylene vinyl acetate copolymers Thermoplastic polyurethanes2.4. Mechanical performance of rings 2.5. Ring insertion and location of ring placement in the vagina 2.6. Changes in cervical/vaginal laxity due to parity and age 2.7. Quantity of fluid in the vaginaendogenous / menstrual / ejaculate 2.8. Concurrent use of vaginal drug products and personal lubricants 2.9. User practices 3. Review of literature on involuntary ring expulsions 3.1. Advice in the event of ring expulsions 3.2. Drug-free rings 3.3. Progesterone and progestogen-only rings Megestrol acetate Levonorgestrel

Pharmacological Approaches for the Prevention of Breast Implant Capsular Contracture

“…Further details of the various fabrication techniques are described in the excellent 2011 review article by Barr et al 43 To those with knowledge and expertise in developing polymeric devices for sustained or controlled release drug administration, it will be apparent that the multi-layer silicone elastomer shell of a breast implant affords opportunities for incorporating and releasing drug substances. Multi-layer or multi-component silicone elastomer devices are currently marketed (or have previously been marketed) for drug delivery applications, including various reservoir-type drug-releasing vaginal rings (e.g., Estring, Femring, Annovera), 44,45 subdermal implants (Norplant, Jadelle), 46 and intrauterine devices (e.g., Mirena, Skyla, Liletta). 47 One such approach would be to disperse or dissolve one or more solid drug substances in the supplied silicone elastomer dispersion formulations, such that, after dipping and curing, the drug(s) would be contained in one or more of the cured silicone elastomer layers of the shell.…”

Color, Scent and Size: Exploring Women's Preferences Around Design Characteristics of Drug-Releasing Vaginal Rings

“…The concept of a polymeric vaginal ring device for use in sustaining drug administration to the human vagina was first described in the late 1960s [ 1 ]. Since then, seven ring products—mostly for hormonal contraception and estrogen replacement therapy—have reached market (Estring®, Progering® Fertiring®, Femring®, Annovera™, NuvaRing® and Ornibel®), and many other devices, including various generics and a dapivirine-releasing ring for HIV prevention, have been approved, are progressing through preclinical/clnical testing, or are undergoing regulatory review for market approval [ 2 – 4 ]. In July, 2020, the European Medicines Agency (EMA) announced a positive regulatory opinion on the Dapivirine Vaginal Ring as an HIV prevention option for cisgender women aged 18 and older [ 5 ], and in March 2022 the ring received regulatory approval for use in South Africa.…”

“…Drug-releasing vaginal ring devices with external diameters ranging between 38 and 80 mm have previously been tested in women, although marketed devices are mostly limited to one of three external diameters—54, 55 or 56 mm—irrespective of the polymer type used to construct the ring (Fig. 1 ) [ 2 ]. There is greater variation in ring cross-sectional diameters (4–9 mm), with silicone elastomer rings falling within the upper end of the range (7.6–9.0 mm) and thermoplastic rings (such as NuvaRing® and Ornibel®) fixed at ~ 4 mm (Fig.…”

“…This contrasts strongly with oral dosage forms which often contain highly colored film coatings to improve product appearance and identification, and provide opportunities for enhanced branding and trademarking [ 7 , 11 , 12 ]. Ring-shaped vaginal pessaries for treating pelvic organ prolapse—in addition to being available in a very wide range of sizes (overall diameter 38 to 127 mm [ 2 ]) —are also supplied in a selection of colors, including white, pink, orange and blue [ 13 ]. Discoloration of white-colored rings—both drug-releasing vaginal rings and ring pessaries—during use has also been reported [ 14 – 16 ].…”

Silicone elastomer formulations for improved performance of a multipurpose vaginal ring releasing dapivirine and levonorgestrel

“…1 ), rings containing LNG often display lower than expected mechanical strength ( Murphy et al, 2016 ). The mechanical characteristics of vaginal rings are critical, since they impact the retention of the device in vivo; involuntary expulsion of rings is reported by users of all marketed ring products and can influence user comfort and acceptability ( Boyd et al, 2020 ; McCoy et al, 2019 ). The mechanical properties of marketed rings have been reported and depend on the ring design and type of polymer used ( Fetherston et al, 2013 ; McCoy et al, 2019 ).…”