Surfactant-Mediated Dissolution of Poorly Soluble Drug Substances
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Authors
Buckley, Ryan T.
Issue Date
2005
Type
Thesis
Language
Keywords
Alternative Title
Abstract
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).
Description
44 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.