Intravaginal rings for continuous low-dose administration of cervical ripening agents

Publication date: Available online 24 July 2018Source: International Journal of PharmaceuticsAuthor(s): Yujing Wang, Peter Boyd, Alyson Hunter, R. Karl MalcolmAbstractIntravaginal rings (VRs) have been widely reported for administration of pharmaceutical drugs – most notably estrogens, progestogens and antiretrovirals – to the vagina for clinical benefit. Here, for the first time, we describe the design, manufacture and preclinical testing of VRs for sustained/controlled release of the cervical ripening agents isosorbide mononitrate (ISMN) and misoprostol (MP), either singly or in combination. Matrix-type silicone elastomer VRs containing ISMN showed declining daily release rates, ranging from 31–168 mg (Day 1) to 3–25 mg (Day 11). Novel orifice-type rings, in which a MP-containing silicone elastomer core is partially exposed to the external environment by overmolding with a non-medicated silicone elastomer sheath containing orifices, provided relatively constant daily MP release rates over 14 days (∼20 or 60 μg/day depending on the formulation type). Combination vaginal rings offered simultaneous release of both ISMN and MP over 14 days, with an almost constant MP release rate (60 μg/day) and steadily declining daily ISMN release (295 mg on Day 1 and 24 mg on Day 11). The VR design can be readily tailored to provide sustained or controlled release of ISMN and MP at rates potentially useful for cervical ripening.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research