Development of Hormonal Intravaginal Rings: Technology and Challenges

Abstract

Intravaginal rings (IVRs) are minimally invasive polymeric devices specifically designed to be used for the sustained and prolonged release of various type of drugs such as hormones. One of the benefits of using topical drug delivery systems (e.g., IVRs) is the fact that systemic drug delivery may cause drug resistance due to elevated drug levels. Topical drug delivery also provides higher concentrations of the drug to the target site and has fewer side effects. In addition, when a drug is administered vaginally, the hepatic first-pass effect is avoided, resulting in higher absorption. Contraception and treatments for specific diseases such as endometriosis and hormone deficiencies can be improved by the administration of hormones via an IVR. This article aims to classify and compare various designs of commercially available and non-commercial hormonal IVRs and to analyze their performance. Current challenges affecting the development of IVRs are investigated, and proposed solutions are discussed. A comprehensive search of publications in MEDLINE/PubMed and of commercial product data of IVRs was performed, and the materials, designs, performance, and applications (e.g., contraception, endometriosis, estrogen deficiency and urogenital atrophy) of hormonal IVRs were thoroughly evaluated. Most hormonal IVRs administer female sex hormones, i.e., estrogen and progestogens. In terms of material, IVRs are divided into 3 main groups: silicone, polyurethane, and polyethylene-co-vinyl acetate IVRs. As regards their design, there are 4 major designs for IVRs which strongly affect their performance and the timing and rate of hormone release. Important challenges include reducing the burst release and maintaining the bioavailability of hormones at their site of action over a prolonged period of administration as well as lowering production costs. Hormonal IVRs are a promising method which could be used to facilitate combination therapies by administering multiple drugs in a single IVR while eliminating the side effects of conventional drug administration methods. IVRs could considerably improve womenʼs quality of life all over the world within a short period of time.

Three-Dimensionally Printed Vaginal Rings: Perceptions of Women and Gynecologists in a Cross-Sectional Survey

“…Despite the advantages of the existing VRs, they present some limitations, including increased vaginal secretions, potential for involuntary expulsion, differences in drug absorption, and cultural sensitivities [ 57 , 58 ]. With the objective of overcoming some of these drawbacks and taking into account the flexibility provided by 3D printing in the production of complex shapes, a new design (flat circle) was introduced for the first time in the present study.…”

El anillo vaginal de progesterona como soporte de la fase lútea en fertilización in vitro

“…Debido a que el epitelio vaginal tiene una alta permeabilidad a la P y a la facilidad de aplicación de productos por esta vía, es posible lograr la liberación continua de fármacos con dosis bajas diariamente (16) . Las CV contienen pequeñas partículas de P (PNM), brindando una mayor superficie y mejor absorción.…”

“…La principal característica de las siliconas es su estabilidad química, baja energía en su superficie y el ser hidrofóbicas. Debido a su biocompatibilidad y baja toxicidad, las siliconas son ampliamente utilizadas en la fabricación de productos médicos que permanecen en contacto directo con el cuerpo humano (16) .…”

Modified Free Volume Theory for Self-Diffusion of Small Molecules in Amorphous Polymers

“…Diffusion of small species within polymeric matrices represents a field of growing technical importance to various industrial applications. Particularly in formulation technologies, diffusion of active ingredients in polymers gains practical relevance for ensuring the physical stability of pharmaceutical amorphous solid dispersions, controlled pesticide release from polymers, , design of intravaginal drug delivery systems, , and development of insecticide-impregnated mosquito nets . The free volume theory (FVT) of Vrentas and Duda , offers an efficient predictive approach for estimating the self-diffusivity of small molecules in amorphous non-cross-linked polymers, proven to be consistent with experimental data on multiple occasions. , However, shortcomings such as appearance of negative values of specific hole free volume and the need for at least two measured diffusivity values leave room for improving this model.…”