Evaluation and optimization of progesterone release from intravaginal rings using response surface methodology

IGNACIO M. HELBLING; JUAN C.D. IBARRA; JULIO A. LUNA

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

EDITIONS SANTE

Año: 2015 vol. 29 p. 218 - 225

1773-2247

Response surface methodology was successfully used to study effect of formulation parameters onprogesterone release from rings made of ethylene-vinyl acetate copolymers. Significant effects wereestimated by an analyses of variance (ANOVA) and statistical model was constructed. Model predictionsshowed good agreement with experimental data. Results showed that mass of progesterone releasedcan be enhanced by several strategies. In addition, model behavior was compared with previouslyvalidated model reported in the literature obtaining satisfactory results. The statistical model was alsoemployed to optimize formulation parameters with the aim to reach release rate of about3.545 ± 0.020 mg cm2 days1/2. Optimized prototype was tested in vitro. Results showed that optimizedIVR has similar profiles than the commercial silicone device used as reference. Optimized ringwould have several advantages over commercial one like lower initial and residual content of progesteroneand the possibility of recycling rings after their usage avoiding incineration of used device (asin the case of silicone commercial device). Pharmacokinetics studies must be done to corroboratein vivo performance of optimized IVRs made of EVA.