Development and in vitro evaluation of diazepam oil in water microemulsion as parenteral drug delivery system

Abstract

Parenteral o/w microemulsion was prepared to enhance the solubility and stability of diazepam. Soybean oil, tween 20/tween 80 as a surfactant, glycerin/propylene glycol/polyethylene glycol 400 as a cosurfactant and water for injection were used. The results indicated that tween 80 could form o/w microemulsions with glycerin and polyethylene glycol 400. Glycerin was a better cosurfactant than polyethylene glycol 400 while propylene glycol could not form microemulsion. The area of microemulsion in pseudo-ternary phase diagram increased with the increasing weight ratio of surfactant to cosurfactant. The results from dilution and dye solubility tests showed that the microemulsions were o/w type. The mean droplet diameters of microemulsion with and without diazepam were in between 50-100 nm. The size of microimulsion without diazepam decreased with the increasing ratio of surfactant to cosurfactant. And the mean droplet diameter increased after autoclaving. The solubility of diazepam in o/w microimulsions was found to be 10 mg/ml, which was about 200 fold increase compared with the solubility in water. However, the viscosity of microemulsions was high especially when loaded with diazepam. The drug diffusion from microemulsions was sustained more than 48 hours. The amount of drug diffusion increased when increasing the drug concentration in microemulsion. However, the diffusion patterns showed no significant difference (p>0.05) between formulations containing drug 5 mg/ml and 10 mg/ml. The drug diffusion kinetic was best fitted with Weibull model and cube root model. After accelerated stability testing, microemulsions still showed good physical and chemical stability.