Solubilization by cosolvents II: Phenytoin in binary and ternary solvents

The solubility of the poorly water-soluble drug phenytoin in binary and ternary mixtures of cosolvents and water has been found to be adequately described by the log-linear solubility equation, log (S(m)/S(w)) = Σ(in) = 1 (σ(i) f(i)), where S(m) is the solubility of the drug in the solvent mixture, S(w) is the solubility of drug in water, f(i) is the volume fraction of cosolvent and σ(i) is the slope. The rank order of the slopes of the solubilization curves appears to parallel the polarity of the cosolvent. For most of the cosolvents tested, some degree of deviation from ideal solubilizing behavior exists. The amount of deviation depends upon both the type and amount of cosolvent used. The largest deviation is seen when higher volume fractions (0.7-0.9) of cosolvent are used and was greater for ethanol-water systems than the glycol-water systems. The same reasons for nonideal solubility seen in the binary solvent mixtures may be responsible for the nonideality seen in the ternary solvent systems. In spite of the curvature seen in these plots, the log-linear solubility equation can be very useful in estimating the solubility of a drug in water-cosolvent mixtures. If the solubility of the drug in water and pure cosolvent is known, the solubility in water-cosolvent mixtures can be estimated by plotting these two points on semi-log paper and connecting them with a straight line.