Abstract
Intravaginal 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. Matrixtype
silicone elastomer VRs containing ISMN showed declining daily release rates, ranging from 31 to 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 VRs 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.
Original language | English |
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Pages (from-to) | 124–132 |
Number of pages | 9 |
Journal | International Journal of Pharmaceutics |
Volume | 549 |
Early online date | 24 Jul 2018 |
DOIs | |
Publication status | Published - Oct 2018 |