Abstract
Reservoir systems (drug-loaded core surrounded by drug-free membrane) provide long-term controlled drug release. This is especially beneficial for drug delivery to specific body regions including the vagina. In this study, we investigated the potential of reservoir systems to provide high drug release rates over several weeks. The considered model system was an intra-vaginal ring (IVR) delivering progesterone (P4) in the mg/day range using ethylene-vinyl acetate (EVA) as release rate-controlling polymers. To circumvent the high material needs associated with IVR manufacturing, we implemented a small-scale screening procedure that predicts the drug release from IVRs. Formulations were designed based on the solubility and diffusivity of P4 in EVAs with varying vinyl acetate content. High in-vitro P4 release was achieved by (i) high P4 solubility in the core polymer; (ii) high P4 partition coefficient between the membrane and the core; and/or (iii) low membrane thicknesses. It was challenging for systems designed to release comparatively high fractions of P4 at early times to retain a constant drug release over a long time. P4 crystal dissolution in the core could not counterbalance drug diffusion through the membrane and drug crystal dissolution was found to be the rate-limiting step. Overall, high P4 release rates can be achieved from EVA-based reservoir systems
Highlights
Controlled drug delivery systems (CDDSs) are advantageous over conventional dosage forms as they yield more stable plasma profiles, allow for reduced administration frequency, and minimize potential of side-effects [1]
The current study demonstrated that high P4 release rates can be achieved from reservoir systems that use ethylene-vinyl acetate (EVA) as release controlling polymers
To reach the higher release target, an EVA with a vinyl acetate (VA) content of 40% is required in the core
Summary
Controlled drug delivery systems (CDDSs) are advantageous over conventional dosage forms as they yield more stable plasma profiles, allow for reduced administration frequency, and minimize potential of side-effects [1]. While conventional dosage forms release the drug within a comparatively short time frame, CDDSs contain polymers to control drug release and thereby, the onset and duration of the drug’s action in the body. Active pharmaceutical ingredients (APIs) are homogeneously dispersed/dissolved in the release controlling polymer. Ideal reservoir systems contain the dissolved drug in the core polymer together with drug crystals that act as a reservoir [4]. Thereby, constant drug release is achieved over several weeks [5,6,7], months [8,9], to even years [10,11] This makes reservoir systems most desirable for mid- and long-term administration to specific body regions such as the vagina, uterus or eye. The membrane may prevent recrystallization of the active candidate on the surface of the respective device
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
