The solubility of phenytoin in a physiological salt solution

The solubility of phenytoin (PHT) was examined at room temperature (23 degrees C) one hour and 16 hours after solutions were made. PHT was considered to be dissolved if it could be centrifuged at 1500 c g for 30 minutes without loss of supernatant radioactivity produced by 14C-PTH. Radio-labelled PHT dissolved in 50 mM NaOH (pH 12.6) was used as control. One hour after mixing, PHT concentrations greater than 200 microM were incompletely dissolved. Sixteen hours after mixing, concentrations greater than 150 microM were incompletely dissolved. Solutions made with an excess of Na-PHT yielded a supernatant concentration of 105 microM measured 24 hours after mixing. It is concluded that PHT concentrations higher than 105 microM may form supersaturated solutions that remain homogeneous for 16 hours if the total concentration does not exceed 150 microM. The 150 microM solution is considered to be a relatively stable supersaturated solution since the addition of a small amount of Na-PHT caused only a 7% reduction in supernatant radioactivity after 13 hours.