Abstract
The effect ofPluronics (F–68, F–88, F–I08) on the solubility of diazepam in water was studied. How Pluronics affected the compatibility and sorption of diazepam from i.v. admixture solutions and PVC containers were analyzed qualitatively and quantitativel.
The solubility of diazepam in water at 25 °C increased with an increase in the concentration of Pluronics. The more the concentration of Pluronics the higher the solubility of diazepam. The increase of the solubility of diazepam ranked in the order of F-108 >>F-88 > F-68. Micellar solubilization was responsible for the higher solubility. Turbidity was measured to clarify the compatibility of diazepam injection with or without Pluronics diluted with i.v. admixture fields. Pluronic F-108 is the best, which caused little turbidity for all dilutions. The extent of turbidity is ranked in the order of non-Pluronics >> F-68 >> F-88 >>F-108. The compatibility results agree with solubility determinations. The pH value of the admixture determined immediately after dilution was larger than that of the admixture determined 24 hr after preparation. This might be attributed to the precipitation of diazepam occurring after setting for 24 hr. The sorption of diazepam from the i.v. admixture in PVC bags followed biexponential kinetics. Pluronics F-68 can effectively prevent potency loss of diazepam solution stored in P VC bags, compared to Pluronic F-88, F-108, and Tween 80. At least 90% of the initial diazepam concentration was retained for 24 hr storage by adding Pluronic F-68 to the admixture solution. This study suggests that Pluronic surfactants can be used as a vehicle for diazepam injection.
- Received November 11, 1986.
- Accepted April 21, 1987.
- Copyright © Parenteral Drug Association. All rights reserved.
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