Development Evaluation and Optimization of Solid Dispersions and Liquisolid Compacts of Lercanidipine HC1 and Metolazone for the Enhancement of Solubility

Abstract

In the current investigation, it was aimed to develop, evaluate and newlinestatistically optimize the solid dispersions and liquisolid compacts of poorly soluble newlinedrugs, lercanidipine HCl and metolazone for the enhancement of their solubility. newlineThe selected two drugs come under BCS class-II which have low solubility and newlinehigh permeability. Bioavailability of lercanidipine HCl is 10% whereas that of newlinemetolazone is around 50%. Hence, it was proposed to improve their solubility and newlinedissolution rate in turn to have improved bioavailability. newlinePreformulation studies were conducted to identify the drug newlinecharacteristics and to screen the suitable excipients for the formulations. Based on newlinethe number of factors and their levels proposed in the study, Box-Behnken design newlinewas used for development of solid dispersions of lercanidipine HCl and D-optimal newlinedesign was used for optimization of liquisolid compacts of metolazone. UV-Visible newlinespectrophotometric methods were used for the estimation of drug in in-vitro studies. newlineSoluplus, Kolliphor P 407 and PEG 6000 were selected as independent factors for newlinesolid dispersions. In case of liquisolid compacts formulation, Tween 80 and PEG newline600 were selected as non-volatile solvents; Avicel, Fujicalin and Neusilin were newlineselected as carriers whereas Aerosil and Kollidon were used as coating materials. newlineMicromeritic properties, assay, solubility and in-vitro dissolution studies newlinewere performed all the prepared formulations. Characterization studies were newlineperformed by FT-IR and DSC to study the compatibility of drug and excipients. newlineStatistical optimization was done using Design Expert software version 12 by newlinefollowing numerical and graphical optimization techniques. Predicted formula was newlineexperimentally formulated and evaluated in triplicated and relative error newlinedetermined. newlineAndhra University, Visakhapatnam newlineSelected optimized formulations were used for stability studies as newlineper ICH guidelines at 25±2°C/60±5% RH for long term conditions and newline40±2°C/75±5% RH under accelerated conditions for at least 6 months. newlinePharmacokine