ABSTRACT Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs.

Pravastatin, a natural bioactive compound inhibits cholesterol biosynthesis which is isolated from fungus by fermentation process. A rapid, sensitive and robust novel reversed phase-HPLC method with UV detection set at 238 nm was developed and validated for quantification of pravastatin in pure drug form and pharmaceutical formulation (Pravachol). A liquid-liquid extraction technique was applied for the preparation samples and chromatographic separation was performed on Symmetry® C (5pm, 3.9 x 150 mm) column with a retention time of 1.95 min using isocratic elution of mobile phase. The mobile phase used in this work consisted of a mixture of methanol and phosphate buffer (70:30%, v/v, pH 4) which was delivered at a flow rate at 1.5 ml/min. Developed HPLC-UV method was validated for linearity (R² = 0.999), accuracy, precision, sensitivity, system suitability, selectivity, and robustness. Box-Behnken experimental design was applied in the validation of robustness. Three independent variables such as the composition of mobile phase, flow rate and pH of mobile phase were investigated. The results indicated that a slight change in the mobile phase composition and flow rate affects the responses, while pH had no significant effect on the response. Overall, the proposed HPLC-UV method was found to be simple, sensitive, and highly robust for routine analysis of pravastatin.