title: Controlling the hydration rate of a hydrophilic matrix in the core of an intravaginal ring determines antiretroviral release.
abstract: Intravaginal ring technology is generally limited to releasing low molecular weight species that can diffuse through the ring elastomer. To increase the diversity of drugs that can be delivered from intravaginal rings, we designed an IVR that contains a drug matrix encapsulated in the core of the IVR whereby the mechanism of drug release is uncoupled from the interaction of the drug with the ring elastomer. We call the device a flux controlled pump, and it is comprised of compressed pellets of a mixture of drug and hydroxypropyl cellulose within the hollow core of the ring. The pump orifice size and chemistry of the polymer pellets control the rate of hydration and diffusion of the drug-containing hydroxypropyl cellulose gel from the device. A mechanistic model describing the hydration and diffusion of the hydroxypropyl cellulose matrix is presented. Good agreement between the quantitative model predictions and the experimental studies of drug release was obtained. We achieved controlled release rates of multiple antiretrovirals ranging from μg/d to mg/d by altering the orifice design, drug loading, and mass of pellets loaded in the device. This device could provide an adaptable platform for the vaginal drug delivery of many molecules.
authors.affiliation: Department of Bioengineering, University of Utah, 20 S 2030 E, Salt Lake City, UT 84112, United States; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Teller
authors.affiliation: Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States; Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Malaspina
authors.affiliation: Department of Bioengineering, University of Utah, 20 S 2030 E, Salt Lake City, UT 84112, United States.
authors.forename: Rachna
authors.initials: R
authors.lastname: Rastogi
authors.affiliation: Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Clark
authors.affiliation: Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States; Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States; Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States.
authors.forename: Igal
authors.initials: I
authors.lastname: Szleifer
authors.affiliation: Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States; Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, United States; Department of Obstetrics and Gynecology, Northwestern University, 250 E. Superior, Suite 03-2303, Chicago, IL 60611, United States. Electronic address: patrick.kiser@northwestern.edu.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Kiser
mesh_terms: D000282:Administration, Intravaginal; D000465:Algorithms; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives; D003692:Delayed-Action Preparations; D004058:Diffusion; D016503:Drug Delivery Systems; D015195:Drug Design; D005079:Excipients; D005260:Female; D006801:Humans; D008962:Models, Theoretical; D012192:Retroviridae Infections / Q000517:prevention & control*
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D002482:Cellulose; C008079:hydroxypropylcellulose
keywords: Drug release model; Intravaginal ring; Sustained drug release; Vaginal delivery