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

Abstract

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 x 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.

Role of surfactant and pH on dissolution properties of fenofibrate and glipizide—A technical note

“…15,16 The higher molecular weight of Tween 80 (1310 versus 288.4 g/mol) and the greater aggregation weight of its micelles (76 000 versus 15 900 g/mol)…”

Dissolution of Ionizable Water‐Insoluble Drugs: The Combined Effect of pH and Surfactant

“…5 However, this ratio is lower than the ratio of 9.0 observed for the carbamazepine-SLS system. 18 Thus for the PX-SLS system the enhancement in the dissolution rate is the result of the increase in total solubility due to the pH change and solubilization. These results suggest that the dissolution process in vivo, while more complicated due to the more complex and time-dependent environment, can be captured in vitro.…”

Influence of excipients on mixtures containing high amount of dry extract from Aesculus hippocastanum L.

“…In this context, the diffusivity of dissolved specimens (drug molecules and complex moleculemicelle) plays an important role (JAMZAD and FASSIHI, 2006). The diffusivity of the complex drug-micelle is smaller than the molecule itself and change in the rate of dissolution is a result of an increase in solubility plus the decrease in diffusivity (CRISON et al, 1996;BALAKRISHNAN et al, 2004;JAMZAD and FASSIHI, 2006). Due to the high molecular weight of Tween 80 and the great mass of its aggregation micelles in comparison with SLS (TURRO and YEKTA, 1978;NERURKAR et al, 1997;JAMZAD and FASSIHI, 2006), the polysorbate provides low diffusivity of the complex drug-micelle and consequently reduces the rate of dissolution (BALAKRISHNAN et al, 2004;JAMZAD and FASSIHI, 2006).…”