Author : Anita V. Malusare, Kiran G. Sonkambale,Dr. Ramesh G. Katedeshmukh,Amol B. Kumbhar,Shivraj V. Mane,Prashant A. Pawar,Jyoti N. Kadam,
Formulation and evaluation of nanosuspension for enhancing the solubility of poorly soluble Antihyperlipidemic Drugs
European Journal of Molecular & Clinical Medicine,
2021, Volume 8, Issue 3, Pages 913-928
Gemfibrozil is a lipid regulating agent that decreases serum triglycerides and very low density lipoprotein cholesterol and increases high‑density lipoprotein (HDL) cholesterol.
According to the Biopharmaceutical Classification System, GEM is classified under class‑II drugs.Class‑II drugs are the drugs with poor solubility and high permeation in the human body and pose problems in their pharmaceutical product development process. The aim
of this work is to prepare GEM nanosuspensions using a precipitation ultrasonication method to increase its water solubility. The prepared nanosuspension was evaluated for Percent transmitance and in vitro dissolution. A Box behnken design was employed to study the effect of the independent variables i.e drug concentration in organic phase (mg/ml) at levels 20, 50 and 80 mg/ml (X1), Polyvinyl alcohol concentration at 0.1, 0.3 and 0.5 % (X2) and Sonication time at levels 10, 20 and 30 minutes (X3) on the dependent variables (i.e., percentage of drug released after 90min).The resulting data were fitted into Design Expert software and analysed statistically using analysis of variance (ANOVA). The data were also subjected to 3-D response surface methodology to determine the influence of concentration of Drug , PVA concentration and sonication time on dependent variable.The results show that nanosuspensions prepared with the higher concentrations of drug , the higher quantities of PVA and higher sonication time reduced the particle size and enhanced the dissolution rate of the formulation. The dissolution rate of the optimized nanosuspension Formulation was enhanced (96.2% in 90 min) mainly because of the formation of nanosized particles. The particle size of optimized nanosuspension was 191.0 nm and zeta potential was -12mV which is enough for sufficient electrostatic stabilization of Gemfibrozil nanosuspension. The X-ray powder diffraction and differential scanning calorimetry results indicated that the amorphization of gemfibrozil ra crystal and convert into nanocrystalline form and presence of drug. Conclusively, nanosuspension of gemfibrozil prepared using precipitation ultrasonication method showed improved solubility as compare with pure gemfibrozil.
Keywords: Gemfibrozil, Nanosuspension, Precipitation-ultrasonication method, particle size, Solubility, bioavailability.