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.
Method:
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.
Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach
