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.

中文翻译：

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质量通过设计方法开发和表征富马酸喹硫平固体脂质纳米颗粒。

背景技术由于肝首过代谢，第二代抗精神病药富马酸喹硫平具有9％的口服生物利用度。报告表明，将药物与脂质共同使用会影响其吸收途径，增强淋巴运输，从而绕开肝脏首过代谢，从而提高生物利用度。目的本研究旨在通过“按质量设计”方法开发和表征富马酸喹硫平潜在可经淋巴吸收的固体脂质纳米颗粒（SLN）。方法采用热乳化后超声处理作为制备方法。Precirol ATO5，磷脂90G和泊洛沙姆188分别用作脂质，稳定剂和表面活性剂。A32 Central Composite设计优化了2个独立变量，脂质浓度和稳定剂浓度，并评估它们对截留效率百分比的影响（％EE：Y1）。研究了冻干的SLN在5±3°C和25±2°C / 60±5％RH下的稳定性3个月。结果对SLN的优化配方含有270mg的Precirol ATO5和107mg的Phospholipon 90G，％EE值为76.53％。平均粒径为159.8nm，多分散指数为0.273，ζ电势为-6.6mV。体外药物释放遵循Korsmeyer-Peppas动力学（R2 = 0.917），释放指数n = 0.722，表明非菲克扩散。透射电子显微镜图像显示颗粒为球形和光滑。傅里叶变换红外光谱，差示扫描量热法和X射线衍射研究确定了药物与赋形剂的相容性。稳定性研究表明，在适合的温度范围内将5 oC储存和保存重要特性是可以接受的。结论经设计和质量优化开发和优化是合理的，因为它产生了具有可接受特性的SLN，并有望在肠淋巴运输中得到应用。