Vobalaboina Venkateshwarlu

The aim of present work was to enhance the dissolution of poorly soluble drug metaxalone  by particle size reduction. Metaxalone nanoparticles are obtained by high pressure homogenization followed by drying, which are characterized for mean particle size (MPS), polydispersity-index(PDI), zeta-potential(ZP), X-ray diffraction(XRD), Differential scanning calorimetry(DSC), Fourier-transform infra-red(FTIR), scanning electron microscopy (SEM), flow properties, saturation solubility and in-vitro release. The MPS of nanoparticles was observed to be less than 200 nm. The negative ZP indicates the stable nanoparticles obtained by sufficient adsorption of the stabilizers onto drug surface. The XRD and DSC  show the retention of drug crystallinity. Out of three drying methods,  SD and SG have obtained stable nanoparticles with improved flow properties. Nanoparticles increased the drug solubility by approximately 4 folds with Hydroxy propyl methyl cellulose and sodium lauryl sulfate as surface stabilizers. In-vitro release studies showed a remarkable increase in rate of drug release from 3 % (pure drug) to 34-36 % (nanoparticles) after 15 minutes and at the end of dissolution study almost 95 % of drug dissolved when compared to only 30 % of pure drug. The combining methods of HPH followed by SD/SG was observed to be promising method to produce stable nanoparticles of metaxalone with remarkable increase dissolution rate.. Results from this study suggest that these metaxalone nanoparticles may be a potential candidate for oral administration with quick onset of action for relief of acute painful musculoskeletal conditions.                            

In the present study, the optimization of composition and process for preparation of the nanosuspension of quetiapine fumarate (QF) was carried out by using design of experiments (DOE). Quetiapine fumarate (QF) is atypical antipsychotic drug under BCS class II. Due to its poor aqueous solubility, the oral bioavailability is only 9 %. High pressure homogenization (HPH) was used as technique for preparing the nanosuspension. For optimization of the composition and process of QF nanosuspension, the three square (32) factorial design was used. For the composition optimization, concentration of the Polyvinyl pyrrolidone (PVP), sodium lauryl sulphate (SLS) and for process optimization homogenization time, homogenization pressure were 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 further elucidated by response surface plots and contour plots. From the analysis of the data it has been observed that 5.25 % PVP, 0.75 % SLS were optimum concentrations and 750 bar pressure, 90 minutes of homogenization were optimum process conditions. The optimized nano composition prepared using optimized process conditions for preparing QF nanosuspension 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 loss of drug crystallinity. IR has shown drug is compatible with the excipients used. SEM photograph of the spray dried nanoparticles of optimized composition has shown spherical drug nanoparticles. The optimization of the composition and homogenizing process 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.