The effect of protein on the dissolution of phenytoin.

Ultrafiltration of a continuous flow system was used to follow the dissolution of phenytoin powder in buffered solutions of pH 1, 4 and 7.4. The presence of either human serum albumin (HSA) or casein caused changes in both the absolute solubility and the dissolution rate. Normal protein binding cannot be responsible for the effects noted. It would seem likely that within the diffusion layer a higher degree of protein binding occurs than is possible in the bulk aqueous solution. The drug solubilized in this way is then released in solution in a form that is at least metastable with respect to phenytoin in normal solution. The effect of protein on phenytoin dissolution may well affect the bioavailability of the drug.