Abstract
In the case of poorly water-soluble drugs the solubility can be improved by the addition of certain solvents, such as propylene glycol, glycofurol or polyethylene glycols, resulting in an increase of the concentration gradient ΔC. However, one has to take into account at the same time a decrease of the polarity of the solvent-water vehicle, resulting in a decrease of the mass transport coefficient K. The aim of this study was to investigate the influence of these competitive factors on the rectal absorption process in human volunteers, using paracetamol as a poorly soluble model drug. A simple diffusion apparatus was developed in order to measure in vitro diffusion flows of the test drug from various solvent-water mixtures. We conclude that the product of K and ΔC can be seen as an indication to which extent the actual absorption phase will be influenced. Using an in vitro model as described in this study, a sort of optimum in the concentration of the particular solvent used can be established.
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