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

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

AAPS JOURNAL

SPRINGER

Lugar: Berlin; Año: 2016 vol. 18 p. 960 - 971

1550-7416

Burst release was observed when ethylene vinyl acetate copolymer (EVA) intravaginalrings were tested for progesterone release in our previous work (1). Burst release is undesirable incontrolled delivery devices because release is uncontrollable and higher levelsof activepharmaceutical ingredient could lead to the occurrence of adverseeffect. The present contribution is about the use of membranes to coat EVA ringsto eliminate burst release. Physicochemical state of progesterone in uncoatedrings and the solubility and diffusion coefficient in membrane were studied. Hormonedelivery from several rings of different sizes was compared. A mathematicalmodel was used to analyze the effects of membrane properties on delivery rate. Nochemical interactions were detected between hormone and polymer. Hormone was mainlyforming amorphous aggregates inside rings and migration to membrane was notobserved during storage. Diffusion coefficient was smaller in membrane ( ~ 10-8cm2 s-1) than in matrix (~ 10-7 cm2s-1). Zero order release kinetics were obtained for coated rings andrelease rate decreases as the thickness of the coat increases. Cellulosemembrane successfully eliminates burst release and controls the delivery fromEVA rings. The equations developed can be used to determine the appropriatecoat thickness to produce specific release rate.