Surfactant-Mediated Dissolution of Poorly Soluble Drug Substances
Buckley, Ryan T.
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Researchers have developed models that predict dissolution rates for poorly soluble drugs in the presence of solubilizing agents, but these predicted rates vary greatly depending on which model is used. While these models accurately predict dissolution rates for many drugs, they do not accurately predict dissolution rates when surfactants are present. The present study was conducted to elucidate the mechanism by which micellar transport affects dissolution rate. Previous work shows that the rate of dissolution of a poorly soluble drug in the presence of surfactant may not increase linearly after the Critical Micelle Concentration has been achieved, but rather may reach a plateau. One goal of these experiments is to test if this plateau truly exists and by what mechanism the drug reaches this maximum rate. Suspension formulations of the low solubility model drugs griseofulvin and DD2 were delivered to a medium containing surfactant by means of a suspension vehicle. Measured absorbance and time values were used to calculate rate constants for each experiment and these rate constants were then used to compare the individual experiments. The model drugs were run in various concentrations of the surfactants Hexadecyl-trimethyl-ammonium Bromide (CTAB), Polyethylene glycol sorbitan monooleate (Tween-80) and Sodium Dodecyl Sulfate (SDS). This data was fit with a Weibull curve using the program Origin©. The relative dissolution rates were evaluated by comparing the respective rate constants (k) gathered from the curve fittings. In line with previous work, it was found that the rate of dissolution of griseofulvin in the presence of the surfactant Tween-80 approaches a plateau for the drug griseofulvin. It was also found that the presence of monomeric surfactant does increase the dissolution rate despite the absence of micelles (surfactant concentrations under the critical micelle concentration).