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 transpo rt of drug-loaded micelles from a rotating disk. Alternative definitio ns for effective diffusivity and reaction factor are presented and com pared with those commonly used for this type of transport problem. The conventional and alternative approaches are based on the same fundame ntal assumptions differing only in their interpretation of the diffusi onal boundary layer. For example, in this study it was observed that, above the cmc, a 2% w/v solution of sodium lauryl sulfate increased th e dissolution rate approximately 6-fold and the solubility approximate ly 20-fold. This difference between the solubility and dissolution enh ancement was attributed to the contribution to the total transport of both the enhanced solubility, a 20-fold increase, and the effective di ffusivity of the drug-micelle complex, a 3-fold decrease, hence a net 6-fold increase in dissolution. The diffusivity of the drug-loaded mic elle estimated from the dissolution data using the new definitions com pared well with values determined by other methods (D-sm = 8.4 x 10(-7 ) cm(2)/s). On the basis of these results, the new definitions for the effective diffusivity and reaction factor offer a practical method fo r estimating micellar diffusion coefficients and predicting drug disso lution under the well-defined hydrodynamics of the rotating disk. It m ay 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.