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.

Burst release was observed when ethylene vinyl acetate copolymer (EVA) intravaginal rings were tested for progesterone release in our previous work (Helbling et al. Pharm Res. 31(3):795-808, 2014). Burst release is undesirable in controlled delivery devices because release is uncontrollable and higher levels of active pharmaceutical ingredient could lead to the occurrence of adverse effect. The present contribution is about the use of membranes to coat EVA rings to eliminate burst release. Physicochemical state of progesterone in uncoated rings and the solubility and diffusion coefficient in membrane were studied. Hormone delivery from several rings of different sizes was compared. A mathematical model was used to analyze the effects of membrane properties on delivery rate. No chemical interactions were detected between hormone and polymer. Hormone was mainly forming amorphous aggregates inside rings, and migration to membrane was not observed during storage. Diffusion coefficient was smaller in membrane (∼10(-8) cm(2) s(-1)) than in matrix (∼10(-7) cm(2) s(-1)). Zero-order release kinetics were obtained for coated rings, and release rate decreases as the thickness of the coat increases. Cellulose membrane successfully eliminates burst release and controls the delivery from EVA rings. The equations developed can be used to determine the appropriate coat thickness to produce specific release rate.