Drug Dissolution Into Micellar Solutions: Development of a Convective Diffusion Model and Comparison to the Film Equilibrium Model with Application to Surfactant-Facilitated Dissolution of Carbamazepine

The intrinsic dissolution rate of carbamazepine in solutions of sodium lauryl sulfate was measured to study the convective diffusion transport of drug-loaded micelles from a rotating disk. Alternative definitions for effective diffusivity and reaction factor are presented and compared with those commonly used for this type of transport problem. The conventional and alternative approaches are based on the same fundamental assumptions differing only in their interpretation of the diffusional boundary layer. For example, in this study it was observed that, above the cmc, a 2% w/v solution of sodium lauryl sulfate increased the dissolution rate approximately 6-fold and the solubility approximately 20-fold. This difference between the solubility and dissolution enhancement was attributed to the contribution to the total transport of both the enhanced solubility, a 20-fold increase, and the effective diffusivity of the drug–micelle complex, a 3-fold decrease, hence a net 6-fold increase in dissolution. The diffusivity of the drug-loaded micelle estimated from the dissolution data using the new definitions compared well with values determined by other methods (Dsm = 8.4 × 10−7 cm2/s). On the basis of these results, the new definitions for the effective diffusivity and reaction factor offer a practical method for estimating micellar diffusion coefficients and predicting drug dissolution under the well-defined hydrodynamics of the rotating disk. It may also be possible to extend the application of these definitions to study the dissolution of water-insoluble drugs in other media, such as emulsions, to better understand drug dissolution under fed conditions in vivo.