Abstract

The solubility relationships of a non-polar (tioconazole), polar (oxfenieine) and semi-polar (caffeine) drug have been investigated in aqueous ethanol, propylene glycol and polyethylene glycol 400 (PEG 400) binary co-solvent systems. A semi-empirical equation was deduced to describe the relationship between the amount of drug dissolved and the volume fraction of co-solvent employed. The data for tioconazole and oxfenicine followed the expected semi-logarithmic relationship between solubility and fraction co-solvent. However, the semi-polar drug, caffeine followed this relationship only with PEG 400; the other two co-solvents yielded parabolic relationships.Using the binary solubility data, multiple linear regression was used to deduce an equation for the solubility of tioconazole in ternary ethanol, propylene glycol and PEG 400 co-solvent systems. The derived relationship gave excellent prediction of the drug solubility throughout the complete volume fraction range. This allowed a graphical representation of the drug solubility-co-solvent fraction relationship to be established. This visualization of are drug solubility relationship was then used to demonstrate its utility to optimize drug solubility within the competing constraints of the pharmaceutical system.

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