Quetiapine Fumarate

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.

Quetiapine Fumarate is a antipsychotic agent indicated for treatment of Schizophrenia and Bipolar disorder. Quetiapine Fumarate is BCS Class II drug which is  poorly water soluble and may show dissolution limited absorption. Hence to improve dissolution rate and bioavailability, Solid dispersion of Quetiapine Fumarate by Solvent Evaporation method were prepared using 1:1, 1:2, 1:3, 1:4 and 1:5 ratios of Quetiapine Fumarate and Polyvinyl Pyrrolidone K30(PVP K30). The solid dispersion (SD) was characterized for physical appearance, solubility, FTIR, DSC, XRD studies and in vitro dissolution studies. FTIR study revealed that there was no drug-carrier chemical interaction in Solid dispersion. DSC studies revealed that, the peak observed for the melting of Quetiapine Fumarate is found to be absent in SD with PVP K30 carrier. XRD studies suggested that there has been a large change in the nature of Quetiapine Fumarate in the solid dispersion. Solubility of Quetiapine Fumarate from SD increased in distilled water. The drug content was found to be high and uniformly distributed in the formulation. The in vitro dissolution studies were carried using USP type II (paddle) type dissolution apparatus. The prepared Solid dispersion showed marked increase in the dissolution rate of Quetiapine Fumarate than that of pure drug. The Solid dispersion with PVP K30 (1:5) by Solvent evaporation method showed faster dissolution rate as compared to other Solid dispersions. It is concluded that dissolution of the Quetiapine Fumarate could be improved by the Solid dispersion.