title: Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity.
abstract: The objective of this study was to assess the contributions of surfactant-mediated solubility and micellar diffusivity on the ability of surfactant to enhance drug dissolution. The following model was derived to predict the degree to which surfactants enhance griseofulvin dissolution: phi = 1 + (fm/ff).((D(D-M)2/3)/(DD2/3)) where phi is the degree of surfactant-mediated dissolution enhancement, fm is the fraction of the drug in micelle, and ff is the fraction of free drug, and DD and D(D-M) are the diffusivities of free drug and drug-loaded micelles, respectively. The Wood apparatus was used to measure the dissolution of griseofluvin in the presence of the anionic surfactant sodium dodecyl sulfate (SDS), the cationic surfactant cetyl trimethyl ammonium bromide (CTAB), and the neutral surfactants Tween 80 and Cremophor EL. DD was estimated using the Levich equation. D(D-M) was measured using dynamic light scattering. Griseofulvin solubility was evaluated in SDS, CTAB, Tween 80, and Cremophor EL at the surfactant concentrations used in the dissolution studies. DD was 11.0 x 10(-6) cm2/s. D(D-M) was 1.29 x 10(-6) cm2/s, 0.956 x 10(-6) cm2/s, 0.569 x 10(-6) cm2/s, and 0.404 x 10(-6) cm2/s for griseofulvin-loaded micelles of SDS, CTAB, Tween 80, and Cremophor EL, respectively. At the highest surfactant concentrations studied, griseofulvin solubility increased 107-fold, 31-fold, fourfold, and threefold for SDS, CTAB, Tween 80, and Cremophor EL. Dissolution into SDS and CTAB were markedly enhanced, but only about one-third as much as solubility enhancement. Dissolution enhancement in the presence of SDS and CTAB were in excellent agreement with model predicted values, with prediction error less than 12%. The model predicted dissolution into Tween 80 and Cremophor EL to be minimally enhanced, as was observed, although the model underpredicted dissolution into these two neutral surfactants. The derived model predicted surfactant-mediated dissolution and reflects dissolution enhancement to be promoted by surfactant-enhanced solubility, but limited by the relatively slow diffusion of drug-loaded surfactant micelles.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Bhagwant D
authors.initials: BD
authors.lastname: Rege
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
authors.forename: James E
authors.initials: JE
authors.lastname: Polli
mesh_terms: D004058:Diffusion; D006118:Griseofulvin / Q000737:chemistry; D008823:Micelles; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012542:Scattering, Radiation; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D008823:Micelles; D004364:Pharmaceutical Preparations; D013501:Surface-Active Agents; D006118:Griseofulvin