The solubility of phenytoin in a physiological salt solution

The solubility of phenytoin (PHT) was examined at room temperature (23°C) one hour and 16 hours after solutions were made. PHT was considered to be dissolved if it could be centrifuged at 1500 x g for 30 minutes without loss of supernatant radioactivity produced by ¹⁴C-PHT. Radiolabelled PHT dissolved in 50 mM NaOH (pH 12.6) was used as control. One hour after mixing, PHT concentrations greater than 200 μM were incompletely dissolved. Sixteen hours after mixing, concentrations greater than 150 μM were incompletely dissolved. Solutions made with an excess of Na-PHT yielded a supernatant concentration of 105 μM measured 24 hours after mixing. It is concluded that PHT concentrations higher than 105 μM may form supersaturated solutions that remain homogeneous for 16 hours if the total concentration does not exceed 150 μM. The 150 μM 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.