Quality by Design Approach for Development and Characterization of Solid Lipid Nanoparticles of Quetiapine Fumarate.Curr Comput Aided Drug Des 2019CC
Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of extensive hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first pass metabolism resulting in enhanced bioavailability.
The present work was attempted with the aim of developing and characterising potentially lymphatic system absorbable solid lipid nanoparticles (SLN) of Quetiapine fumarate (QF) by Quality by Design approach.
Hot emulsification followed by ultrasonication was used as method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as lipid, stabilizer and surfactant respectively. A 32 Central Composite design (CCD) optimised the 2 independent variables, lipid concentration (X1) and stabilizer concentration (X2) and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The SLN, lyophilized using mannitol, were studied for stability at 5οC ±3 οC and 25 ± 2οC/60 ± 5% RH for 3 months.
The optimised formula derived for SLN had 270mg PrecirolATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetic model (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion . TEM images exhibited particles to be spherical and smooth. FTIR, DSC and XRD studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for SLN storage preserving important characteristics within acceptable limits.
Development and optimisation by Quality by Design was justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.