Formulation and Process Optimization of Quetiapine Fumarate Nanosuspension using Factorial Design

摘要

ABSTRACT 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. Keywords: Quetiapine Fumarate; nanosuspension; particle size, factorial design.