title: An intravaginal ring for the simultaneous delivery of multiple drugs.
abstract: Intravaginal delivery of microbicide combinations is a promising approach for the prevention of sexually transmitted infections, but requires a method of providing simultaneous, independent release of multiple agents into the vaginal compartment. A novel intravaginal ring (IVR) platform has been developed for simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and the guanosine analogue antiviral acyclovir (ACV) with independent control of release rate for each drug. The IVR is based on a pod design, with up to 10 individual polymer-coated drug cores embedded in the ring releasing through preformed delivery channels. The release rate from each pod is controlled independently of the others by the drug properties, polymer coating, and size and number of delivery channels. Pseudo-zero-order in vitro release of TFV (144 ± 10 µg day) and ACV (120 ± 19 µg day⁻¹) from an IVR containing both drugs was sustained for 28 days. The mechanical properties of the pod IVR were evaluated and compared with the commercially available Estring® (Pfizer, NY, NY). The pod-IVR design enables the vaginal delivery of multiple microbicides with differing physicochemical properties, and is an attractive approach for the sustained intravaginal delivery of relatively hydrophilic drugs that are difficult to deliver using conventional matrix IVR technology.
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, Pasadena, California 91107, USA.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Baum
authors.forename: Irina
authors.initials: I
authors.lastname: Butkyavichene
authors.forename: Joshua
authors.initials: J
authors.lastname: Gilman
authors.forename: Sean
authors.initials: S
authors.lastname: Kennedy
authors.forename: Etana
authors.initials: E
authors.lastname: Kopin
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Malone
authors.forename: Cali
authors.initials: C
authors.lastname: Nguyen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Smith
authors.forename: David R
authors.initials: DR
authors.lastname: Friend
authors.forename: Meredith R
authors.initials: MR
authors.lastname: Clark
authors.forename: John A
authors.initials: JA
authors.lastname: Moss
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage*; D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D063065:Organophosphonates / Q000008:administration & dosage*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D012825:Silicon / Q000737:chemistry; D000068698:Tenofovir; D013718:Tensile Strength
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine; D000212:Acyclovir; D012825:Silicon