title: In vitro release properties of etonogestrel and ethinyl estradiol from a contraceptive vaginal ring.
abstract: The release properties of steroids from a combined contraceptive vaginal ring have been investigated. The product design is based on a coaxial fiber consisting of two types of polyethylene vinylacetate copolymers. Inside the core of the fiber, two steroids are present in a molecularly dissolved state. In order to design a controlled release system with specified release characteristics, values of diffusion coefficient and solubility are required. These data can either be determined during pre-formulation studies on e.g. polymeric flat films or from in-vitro release measurements of the actual coaxial fibers. It can be concluded from this study that polyethylene vinylacetate copolymers exhibit suitable properties to develop a controlled release system with the two steroids etonogestrel and ethinyl estradiol. It has been found that the permeability data obtained in the pre-formulation studies are useful in semi-quantitative terms, but deviate from the permeability data found from the in-vitro release of coaxial fibers. This is most likely due to differences in the polymeric structure of films and coaxial fibers. As a consequence, further studies should be initiated to evaluate the relationship between the manufacturing process and the resulting polymeric structure. It has also been found that the solubility and release of etonogestrel are influenced by the concentration of ethinyl estradiol. By investigating this phenomenon by thermoanalysis, it was shown that the steroids form an eutectic. The lower melting point of the steroids results in an increase in solubility and hence in altered permeability properties.
authors.affiliation: Department of Pharmaceutics, N.V. Organon, AKZO-NOBEL, P.O. Box 20, 5340, BH, Oss, The Netherlands. j.laarhoven@organon.oss.akzonobel.nl
authors.forename: J A H
authors.initials: JA
authors.lastname: van Laarhoven
authors.forename: M A B
authors.initials: MA
authors.lastname: Kruft
authors.forename: H
authors.initials: H
authors.lastname: Vromans
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000737:chemistry*; D003274:Contraceptive Devices, Female; D003692:Delayed-Action Preparations; D017135:Desogestrel; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D014753:Vinyl Compounds; C044815:etonogestrel; D004997:Ethinyl Estradiol; D017135:Desogestrel