Optimization of Composition and Process for Preparing Metaxalone Nanosuspension using Factorial Design

Abstract

In the current study, the composition and process for preparing the nanosuspension of metaxalone (MX) has been optimized by using design of experiments (DOE). MX is skeletal muscle relaxant and belongs to BCS class II1 , the class wherein invivo drug dissolution is a rate-limiting step for drug absorption2 . High pressure homogenization (HPH) method was used to prepare the nanosuspension and Hydroxy propyl methyl cellulose (HPMC) and sodium lauryl sulfate (SLS) as surface stabilizers. For optimization studies three square (32 ) factorial design was used. For the composition optimization, concentration of the stabilizers and for process optimization homogenization time and pressure are used as independent variables. The dependent variables were particle size (PS), polydispersity index (PDI), zeta potential (ZP). The relationship between the dependent and independent variables was studied by response surface plots and contour plots. From the data it has been observed that 2.5 % HPMC, 0.5 % SLS were optimum concentrations and 1000 bar pressure, 120 minutes of homogenization were optimum process conditions producing least PS, PDI and high zeta potential. The optimized nano composition prepared by using optimum process conditions was observed to release more than 80 % within 30 minutes and found to be stable after 3 months of storage at room temperature. The solid state characterization (XRD, DSC) data of spray dried nanoparticles of the optimized composition has shown retention of drug crystallinity. IR has shown drug is compatible with the excipients used. SEM photograph has shown spherical drug nanoparticles. The optimization studies by applying the DOE resulted in considerable decrease in the experimentation work to achieve the stable nanosuspension with desired parameters such as PS, PDI and ZP.