title: The optimization of an intravaginal ring releasing progesterone using a mathematical model.
abstract: OBJECTIVE
  Progering® is the only intravaginal ring intended for contraception therapies during lactation. It is made of silicone and releases progesterone through the vaginal walls. However, some drawbacks have been reported in the use of silicone. Therefore, ethylene vinyl acetate copolymer (EVA) was tested in order to replace it.
  
  
  METHODS
  EVA rings were produced by a hot-melt extrusion procedure. Swelling and degradation assays of these matrices were conducted in different mixtures of ethanol/water. Solubility and partition coefficient of progesterone were measured, together with the initial hormone load and characteristic dimensions. A mathematical model was used to design an EVA ring that releases the hormone at specific rate.
  
  
  RESULTS
  An EVA ring releasing progesterone in vitro at about 12.05 ± 8.91 mg day(-1) was successfully designed. This rate of release is similar to that observed for Progering®. In addition, it was observed that as the initial hormone load or ring dimension increases, the rate of release also increases. Also, the device lifetime was extended with a rise in the initial amount of hormone load.
  
  
  CONCLUSIONS
  EVA rings could be designed to release progesterone in vitro at a rate of 12.05 ± 8.91 mg day(-1). This ring would be used in contraception therapies during lactation. The use of EVA in this field could have initially several advantages: less initial and residual hormone content in rings, no need for additional steps of curing or crosslinking, less manufacturing time and costs, and the possibility to recycle the used rings.
authors.affiliation: Laboratorio de Química Fina, Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), Universidad Nacional del Litoral and Consejo Nacional de Investigaciones Científicas y Técnicas, CCT CONICET-SANTA FE, Paraje El Pozo, 3000, Santa Fe, Argentina, ihelbling@santafe-conicet.gov.ar.
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Helbling
authors.forename: Juan C D
authors.initials: JC
authors.lastname: Ibarra
authors.forename: Julio A
authors.initials: JA
authors.lastname: Luna
mesh_terms: D000282:Administration, Intravaginal; D003274:Contraceptive Devices, Female; D004058:Diffusion; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005260:Female; D006801:Humans; D008956:Models, Chemical; D011145:Polyvinyls / Q000737:chemistry*; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D012995:Solubility
chemical_list: D011145:Polyvinyls; D011372:Progestins; C016438:ethylenevinylacetate copolymer; D011374:Progesterone