Design, Development and Optimization of Valsartan Liquisolid Tablets Using Box-behnken Design

The aim of the present study was to investigate the applicability of liquisolid technique in improving the dissolution properties of Valsartan in a solid dosage form. This study was designed to optimize and evaluate the effects of different formulation variables: amount of liquid vehicle (X1), ratio of carrier to coating material(X2) and amount of magnesium oxide(X3) on angle of repose (Y1), hardness(Y2) and in-vitro release(Y3) of formulation using three level three factor Box-Behnken statistical design. The non-linear quadratic model generated by the design is of the form: Y = A0 + A1X1 + A2X2 + A3X3 + A4X1X2 + A5X2X3 + A6X1X3 + A7X1 2 + A8X2 2 +A9X3 2 + E, where Y is the measured response associated with each factor level combination. Contour and response surface plots were depicted based on the equation given by the model. The optimization procedure generated the maximum overall desirability value. The optimized formula yields observed values close to the predicted values. Furthermore, the commonly used carrier and coating materials in liquisolid systems Avicel and Aerosil were replaced by Neusilin, an amorphous magnesium aluminometasilicate with an extremely high specific surface area of 339 m/g to improve the efficiency of liquisolid approach. INTRODUCTION: The poor dissolution rate of water insoluble drugs is still a substantial problem confronting the pharmaceutical industry. A great number of new and, possibly, beneficial chemical entities do not reach the public merely because of their poor oral bioavailability due to inadequate dissolution. Over the years, various solid dosage formulation techniques, to enhance the dissolution of poorly soluble substances, have been introduced with different degrees of success. The technique of ‘liquisolid compacts’ is a new and promising addition towards such a novel aim . Liquisolid compacts are acceptably flowing and compressible powdered forms of liquid medications. The term ‘liquid medication’ implies oily liquid drugs and solutions or suspensions of water insoluble solid drugs carried in suitable nonvolatile solvent systems termed the liquid vehicles. Using this new formulation technique, a liquid medication may be converted into a dry-looking, nonadherent, free flowing and readily compressible powder by a simple blending with selected powder excipients referred to as the carrier and coating materials.