title: Controlling levonorgestrel binding and release in a multi-purpose prevention technology vaginal ring device.
abstract: Despite a long history of incorporating steroids into silicone elastomers for drug delivery applications, little is presently known about the propensity for irreversible drug binding in these systems. In this study, the ability of the contraceptive progestin levonorgestrel to bind chemically with hydrosilane groups in addition-cure silicone elastomers has been thoroughly investigated. Cure time, cure temperature, levonorgestrel particle size, initial levonorgestrel loading and silicone elastomer type were demonstrated to be key parameters impacting the extent of levonorgestrel binding, each through their influence on the solubility of levonorgestrel in the silicone elastomer. Understanding and overcoming this levonorgestrel binding phenomenon is critical for the ongoing development of a number of drug delivery products, including a multi-purpose technology vaginal ring device offering simultaneous release of levonorgestrel and dapivirine - a lead candidate antiretroviral microbicide - for combination HIV prevention and hormonal contraception.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
authors.forename: Diarmaid J
authors.initials: DJ
authors.lastname: Murphy
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Boyd
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
authors.forename: Clare F
authors.initials: CF
authors.lastname: McCoy
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD, United States.
authors.forename: Jonathon D S
authors.initials: JD
authors.lastname: Holt
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD, United States.
authors.forename: Wendy
authors.initials: W
authors.lastname: Blanda
authors.affiliation: International Partnership for Microbicides, Silver Spring, MD, United States.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Brimer
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom. Electronic address: k.malcolm@qub.ac.uk.
authors.forename: R Karl
authors.initials: RK
authors.lastname: Malcolm
mesh_terms: D001665:Binding Sites; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D003274:Contraceptive Devices, Female; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D012826:Silicone Elastomers / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility
chemical_list: D003271:Contraceptive Agents, Female; D012826:Silicone Elastomers; D016912:Levonorgestrel
keywords: Controlled release; Drug delivery; Hydrosilylation; Implantable devices; Silicone elastomer; Vaginal ring