The Use of Cellulose Membrane to Eliminate Burst Release from Intravaginal Rings

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

AAPS JOURNAL

SPRINGER

Lugar: Berlin; Año: 2016

1550-7416

Burst release was observed when ethylene vinyl acetate copolymer (EVA)intravaginal rings were tested for progesterone release in our previous work (Helblinget al. Pharm Res. 31(3):795?808, 2014). Burst release is undesirable in controlled deliverydevices because release is uncontrollable and higher levels of active pharmaceuticalingredient could lead to the occurrence of adverse effect. The present contribution is aboutthe use of membranes to coat EVA rings to eliminate burst release. Physicochemical state ofprogesterone in uncoated rings and the solubility and diffusion coefficient in membrane werestudied. Hormone delivery from several rings of different sizes was compared. Amathematical model was used to analyze the effects of membrane properties on deliveryrate. No chemical interactions were detected between hormone and polymer. Hormone wasmainly forming amorphous aggregates inside rings, and migration to membrane was notobserved during storage. Diffusion coefficient was smaller in membrane (∼10−8 cm2 s−1) thanin matrix (∼10−7 cm2 s−1). Zero-order release kinetics were obtained for coated rings, andrelease rate decreases as the thickness of the coat increases. Cellulose membrane successfullyeliminates burst release and controls the delivery from EVA rings. The equations developedcan be used to determine the appropriate coat thickness to produce specific release rate.