Background: Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability
of 9% because of 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.
Objective: The present work aimed at developing, and characterising potentially lymphatic absorbable Solid
Lipid Nanoparticles (SLN) of quetiapine fumarate by Quality by Design approach.
Methods: Hot emulsification followed by ultrasonication was used as a method of preparation. Precirol
ATO5, Phospholipon 90G and Poloxamer 188 were used as a lipid, stabilizer and surfactant respectively.
A32 Central Composite design optimised the 2 independent variables, lipid concentration and stabilizer
concentration and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The lyophilized
SLNs were studied for stability at 5 ±3οC and 25 ± 2οC/60 ± 5% RH for 3 months.
Results: The optimised formula derived for SLN had 270mg Precirol ATO5 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 kinetics (R2=0.917) with release exponent
n=0.722 indicating non-Fickian diffusion. Transmission electron microscopy images exhibited particles
to be spherical and smooth. Fourier-transform infrared spectroscopy, differential scanning calorimetry
and X-ray diffraction studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as
appropriate temperature for storage and preserving important characteristics within acceptable limits.
Conclusion: Development and optimisation by Quality by Design were justified as it yielded SLN having
acceptable characteristics and potential application for intestinal lymphatic transport.