Phenytoin sodium solubility in three intravenous solutions

The solubility of phenytoin sodium injection of two manufacturer's was studied in three intravenous fluids, 0.9% sodium chloride, lactated Ringer's, and four manufacturers 5% dextrose injections. Phenytoin sodium for injection was added to 250 ml of an intravenous fluid to give calculated initial concentrations of 0.40, 0.98, 2.38, and 4.55 mg/ml. The pH of each solution was determined before and after the addition of phenytoin. Visual examination and nephelometric measurements for crystals were performed at various times between 5 and 1440 minutes after mixing. Phenytoin concentration was determined by spectrophotometry at these times; nephelometric measurements were done on unfiltered samples. The concentration of phenytoin declined rapidly in all dextrose solutions but at different rates for each brand. A greater stability was demonstrated when phenytoin was diluted in 0.9% sodium chloride and lactated Ringer's injections. Mean concentrations in excess of 95% of initial concentration were maintained for eight hours in those fluids. The two brands of phenytoin sodium injection did not differ consistently with respect to solubility. Crystals were observed in all dextrose solutions; nephelometric measurements indicated crystals were present in all solutions. The pH of all solutions increased sharply upon addition of phenytoin sodium injection. It is concluded that 0.9% sodium chloride and lactated Ringer's injections are suitable diluents for the intravenous administration of phenytoin. Factors other than pH and cosolvent concentration may affect phenytoin stability in dextrose solutions.