D-Optimal Design Based Statistical Optimization of Liquisolid Compacts of Lercanidipine Hcl for Enhancement of Solubility

Abstract

In the current investigation, it was aimed to develop, evaluate and statistically optimize the liquisolid compacts of poorly soluble drug, lercanidipine HCl for the enhancement of their solubility. The selected drug come under BCS class-II which have low solubility and high permeability. Bioavailability of lercanidipine HCl is 10% . Hence, it was proposed to improve their solubility and dissolution rate in turn to have improved bioavailability.             Preformulation studies were conducted to identify the drug characteristics and to screen the suitable excipients for the formulations. Based on the number of factors and their levels proposed in the study, D-optimal design was used for optimization of liquisolid compacts of lercanidipine HCl. UV-Visible spectrophotometric methods were used for the estimation of drug in in-vitro studies. For liquisolid compacts formulation, Tween 80 and PEG 600 were selected as non-volatile solvents; Avicel, Fujicalin and Neusilin were selected as carriers whereas Aerosil and Kollidon were used as coating materials.

Micromeritic properties, assay, solubility and in-vitro dissolution studies were performed all the prepared formulations. Characterization studies were performed by FT-IR and DSC to study the compatibility of drug and excipients. Statistical optimization was done using Design Expert software version 12 by following numerical and graphical optimization techniques. Predicted formula was experimentally formulated and evaluated in triplicated and relative error determined.  Selected optimized formulations were used for stability studies as per ICH guidelines at 25±2°C/60±5% RH for long term conditions and 40±2°C/75±5% RH under accelerated conditions for at least 6 months. The studies reveal that the development of liquisolid compacts is a versatile process to attain the proposed target of enhancement of solubility and dissolution rate.  Hence, it was concluded that the development of   liquisolid compacts of lercanidipine HCl   addresses the solubility   problem of   the drug. Scale up of the proposed methods is also industrially possible and can be explored further to proceed for commercial industrial application.