Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

Abstract

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.

Pharmacokinetics and Pharmacodynamics of Curcumin-Loaded Solid Lipid Nanoparticles in the Management of Streptozotocin-Induced Diabetes Mellitus: Application of Central Composite Design

“…The PDI near 0 is considered suitable for homogeneous distribution of SLNs and considered acceptable up to 0.5 for narrow size distribution. 45 In our study, PDI was found to be decreased by increasing the surfactant concentration (Table 2). The reasons may same as for particle size.…”

“…The optimized formulation was stored at 25°C -2°C/ 60% -5% and 40°C -2°C/75% -5% temperature/relative humidity for 180 days and checked at regular intervals for particle size, PDI, and entrapment efficiency. 45…”

Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain

“…As shown in Table 3, the drug release exponent (n) was 0.5548 and 0.5579 for NLC Riluzole and functionalized NLC, respectively. Given that 0.45 < n < 0.89, the release can be categorized as anomalous or non-Fickian diffusion, where a combined pattern of both diffusion and lipid erosion may be involved in the transport mechanism [48,49]. Nonetheless, since the value of n is closer to the lower range of the interval (i.e., to 0.45), it can be considered that the release is mainly governed by diffusion.…”

<p>Deformable Liposomal Hydrogel for Dermal and Transdermal Delivery of Meloxicam</p>

“…In the present study, zeta potential has been employed to estimate the surface charge. As many studies revealed, 55–57 higher positive or negative values of zeta potential of nano vesicles indicate good physical stability due to electrostatic repulsion of individual particles. On the other hand, zeta potential value close to zero can result in particle aggregation and flocculation due to the van der Waals attractive forces.…”