Crystallization of three phenytoin preparations in intravenous solutions

The stability of three phenytoin sodium intravenous preparations in two intravenous solutions was compared. Solutions of phenytoin sodium 1.0, 1.5, 4.0. and 10.0 mg/ml were prepared by adding Dilantin, Phenhydan (commercially available in Europe) and Phenytoin Concentrate (available in Europe for research) to 5% dextrose or 0.9% sodium chloride injection. (The two European products contain solubilizers and stabilizers different from those in U.S. formulations.) Four sets of samples were prepared in 10-ml glass blood collection tubes; two sets each were sealed and unsealed. Macroscopic and microscopic observations were made immediately and at various times up to 24 hours. The pH was measured periodically. The three phenytoin sodium preparations also were added to 100-ml polyvinyl chloride bags of 5% dextrose or 0.9% sodium chloride injection in concentrations of 1, 1.5, 4, and 10 mg/ml. Phenytoin concentration was determined spectrophotometrically initially and at 1, 4, 8, 12, and 24 hours. Percent phenytoin crystallization, based on initial concentration, was calculated, and differences among the three phenytoin products were tested using an analysis of variance split-plot factorial design (p less than 0.05). Dilutions of Phenhydan and Phenytoin Concentrate in both solutions were stable (less than 10% crystallization) for at least 24 hours. Percent phenytoin crystallization was significantly greater for Dilantin compared with Phenhydan or Phenytoin Concentrate at each time in 5% dextrose injection and after four hours in 0.9% sodium chloride injection. Phenytoin crystallization was not solely dependent on pH of the solution, concentration, or carbon dioxide absorption. Phenhydan and Phenytoin Concentrate admixtures provided a more suitable environment for phenytoin stability than Dilantin admixtures did.