particle size

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.

Aceclofenac is a non steroidal anti- inflammatory drug characterized by low solubility and high permeability which corresponds to BCS class II drug. The strategy of increasing the in vitro dissolution has the potential to enhance the oral bioavailability when using nanosized crystalline drugs. The purpose of this study was to evaluate a novel in situ micronization method avoiding any milling techniques to produce nano- or microsized drug particles by controlled crystallization to enhance the dissolution rate of poorly water-soluble drugs. Aceclofenac microcrystals were prepared by the association of the previously molecularly dispersed drug using a rapid solvent change process. The drug was precipitated in the presence of stabilizing agents, such as hydrocolloids. The obtained dispersion was spray-dried. Particle size, morphology, flow property, zeta potential and dissolution rate were analyzed. Physicochemical properties were characterized using differential scanning calorimetry and X-ray diffractometry. The obtained dispersions showed a homogeneous particle size distribution. Drugs are obtained in a mean particle size of approximately 3µm and below. A high specific surface area was created and in situ stabilized. The surface was hydrophilized because of the adsorbed stabilizer. The solubility of the drug was increased by 2 folds. Thus, a drug powder with markedly enhanced dissolution rate was obtained. In situ micronization is a suitable method for the production of micro-sized drugs. This technique can be performed continuously or discontinuously and uses only common technical equipment. Compared to milled products drug properties are optimized as all particle surfaces are naturally grown, the particle size is more uniformly distributed and the powder is less cohesive.