Influence of process route on the mechanical properties of polymer based intravaginal drug delivery systems

Abstract

Intravaginal rings (IVRs) are designed for controlled release of one or more active pharmaceutical ingredients (APIs) to the vaginal tract, and finally into systemic circulation over extended time periods [1]. The concept is built on the principle of using polymers as the carrier, in which the APIs show a certain permeability, yielding specific release rates [2, 3]. Technologically, IVRs are classified into matrix and reservoir types. In matrix systems, the API is homogeneously dispersed throughout the polymer. A route to produce matrix IVRs is hot melt extrusion to obtain drug-loaded polymer intermediates, which are then injection-molded to yield the ring shape. In a reservoir system, the polymer core contains the homogeneously dispersed API and is surrounded by a drug-free skin. The production route of reservoir systems includes co-extrusion of the layered structure (drug-loaded core, drug-free skin), followed by a joining process to obtain the ring. The IVR’s mechanical characteristics are critical for its application. Other than performing side-by-side comparison tests with existing products which have demonstrated high user acceptability, there is no model to directly determine the ideal range for mechanical IVR acceptability. This is due to the wide range of vaginal shapes and sizes among the female user population. Under normal physiological conditions, the vaginal tract is a low-friction environment due to the presence of vaginal fluid and cervicovaginal mucus. The IVR ring is required to be flexible. Prior to and during insertion, the IVR has to be easily compressed, followed by fast recovery, to remain in the vaginal cavity without causing damage. Yet, the junction deriving from the ring closure needs to be strong enough to prevent ring opening. An IVR’s mechanical properties can be changed via its formulation. In this study, the impact of process parameters, polymers used (polymer crystallinity) and their content on the mechanical properties of EVA-based rings was investigated.