Shweta Agarwal*, Rayasa S. Ramachandra Murthy, Sasidharan Leelakumari Harikumar and Rajeev Garg Pages 73 - 91 ( 19 )
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.
Quetiapine fumarate, solid lipid nanoparticles, percent entrapment efficiency, precirol ATO5, phospholipon 90G, quality by design.
IKG Punjab Technical University, Kapurthala, Department of Pharmacy, Maharaja Sayajirao University, Baroda, Vadodara, Central University of Jharkhand, Ranchi, Department of Pharmaceutics, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela, Ropar