Solubility characteristics of diazepam in aqueous admixture solutions: theory and practice.

The solubility of diazepam was investigated to determine compatibility limits for diluting diazepam injection in four large-volume parenteral (LVP) solutions. A solution of diazepam powder (15 mg/ml) in absolute alcohol and of the commercially available diazepam injection (5 mg/ml) were used in the study. Either 1.0 ml of the alcoholic solution or 3.0 ml of the commercial injection were added to 50 ml of the LVPs studied-sterile water for injection (WFI), 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection. Diazepam was assayed sprectrophotometrically at 367 nm. The solubility of diazepam in WFI was 0.041 mg/ml after equilibration for 24 hours at 25 degrees C. The solubility of diazepam in the LVPs ranged from 0.04 to 0.05 mg/ml at 25 degrees C. The effects of solution dielectric constants on nonelectrolyte solubility and the minimal fraction of protonated (ionized) diazepam present in typical admixtures are deduced to be negligible determinants of diazepam solubility in i.v. solutions at pH greater than or equal to 5.4 prepared from greater than or equal to 1:10 volume dilutions of diazepam injection. The aqueous solubility data for diazepam corroborate other reported values and are tantamount to recommending against less than a 1:100 volume dilution of diazepam injection when compounding i.v. admixtures.