title: Controlled release of estradiol solubilized in carbopol/surfactant aggregates.
abstract: The potential of carbopol/surfactant dispersions as solubilizing and controlled release systems of estradiol (a poorly water-soluble drug) was evaluated. The solubilization of estradiol in the dispersions of Carbopol 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.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Barreiro-Iglesias
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
mesh_terms: D000180:Acrylic Resins; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004958:Estradiol / Q000737:chemistry / Q000493:pharmacokinetics*; D011145:Polyvinyls / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D011145:Polyvinyls; D013501:Surface-Active Agents; C006912:carboxypolymethylene; D004958:Estradiol