Controlled release of estradiol solubilized in carbopol/surfactant aggregates

The potential of carbopol/surfactant dispersions as solubilizing and controlled release systems of estradiol (a poorly watersoluble drug) was evaluated. The solubilization of estradiol in the dispersions of Carbopol(R) 934 (0.25%) and Pluronic F-127, Tween 80, sodium dodecylsulfate (SDS), or benzalkonium chloride (BkCl) was assessed, by differential scanning calorimetry (DSC) of films obtained by desiccation, as a decrease in estradiol melting temperature and enthalpy. The amounts of estradiol solubilized in carbopol/SDS and carbopol/Tween 80 aqueous dispersions were considerably greater (solubilization capacity: 1.3 and 9 times greater) than in the surfactant alone solutions and up to 100 times greater than in water. High aggregates/water equilibrium partition coefficients of estradiol in carbopol/SDS (1768 M-1) and carbopol/Tween 80 (14114 M-1) dispersions were found. Carbopol/(1%) SDS/(25 mg/dl) estradiol and carbopol/(0.1%) Tween 80/(5 mg/dl) estradiol dispersions had a pH of around 4, were easy flowing, and showed sustained release for at least 1 week. Estradiol diffusion coefficients were greater when the receptor medium was 0.3-1.0% SDS solution than when it was iso-osmotic NaCl solution or pH 7.5 phosphate buffer. At this pH, a viscoelastic gel is formed on the donor side of the membrane and the drug diffusion slowed down. When the receptor medium contains a surfactant, estradiol release seems to happen as a direct exchange between the carbopol/surfactant aggregates and the receptor surfactant micelles. If no surfactant is in the receptor fluid, estradiol/surfactant complexes migrate towards the receptor. Despite the low viscosity of these dispersions, estradiol diffusion coefficients were in the same order of magnitude as those obtained with a commercially available neutralized ethanol/water carbopol gel of estradiol (60 mg/dl). When the receptor medium had no surfactant, the low affinity of estradiol for water prevented drug diffusion from the commercial formulation. In summary, carbopol/surfactant aggregates act as efficient carriers of hydrophobic drugs; the affinity of estradiol for carbopol/surfactant aggregates, their dissociation, and the diffusivity of estradiol/surfactant complexes being key factors in the control of the drug release process. (C) 2003 Elsevier B.V. All rights reserved.