title: Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel.
abstract: A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception.
authors.affiliation: School of Pharmacy, Queen⿿s University Belfast, Belfast BT9 7BL, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Boyd
authors.affiliation: QPharma, Malmo, Sweden.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fetherston
authors.affiliation: School of Pharmacy, Queen⿿s University Belfast, Belfast BT9 7BL, UK.
authors.forename: Clare F
authors.initials: CF
authors.lastname: McCoy
authors.affiliation: Athlone Institute of Technology, Athlone, Ireland.
authors.forename: Ian
authors.initials: I
authors.lastname: Major
authors.affiliation: School of Pharmacy, Queen⿿s University Belfast, Belfast BT9 7BL, UK.
authors.forename: Diarmaid J
authors.initials: DJ
authors.lastname: Murphy
authors.affiliation: School of Pharmacy, Queen⿿s University Belfast, Belfast BT9 7BL, UK.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD 20910, USA.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Holt
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD 20910, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brimer
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD 20910, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Blanda
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD 20910, USA.
authors.forename: Brid
authors.initials: B
authors.lastname: Devlin
authors.affiliation: School of Pharmacy, Queen⿿s University Belfast, Belfast BT9 7BL, UK. Electronic address: k.malcolm@qub.ac.uk.
authors.forename: R Karl
authors.initials: RK
authors.lastname: Malcolm
mesh_terms: D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003274:Contraceptive Devices, Female; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D065546:Drug Liberation / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D016912:Levonorgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D011743:Pyrimidines; D016912:Levonorgestrel; D054303:HIV Reverse Transcriptase; C481671:Dapivirine
keywords: Formulation development; HIV microbicide; Hormonal contraception; MPT; Multipurpose prevention technology; Silicone elastomer vaginal ring