Zaki Randa Mohammed, Alfadhel Munerah M, Alossaimi Manal A, Elsawaf Lara Ayman, Devanathadesikan Seshadri Vidya, Almurshedi Alanood S, Yusif Rehab Mohammad, Said Mayada
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef P.O. Box 62514, Egypt.
Pharmaceuticals (Basel). 2022 Jul 29;15(8):940. doi: 10.3390/ph15080940.
This study aimed to formulate and statistically optimize glycerosomal formulations of Quetiapine fumarate (QTF) to increase its oral bioavailability and enhance its brain delivery. The study was designed using a Central composite rotatable design using Design-Expert software. The independent variables in the study were glycerol % / and cholesterol % /, while the dependent variables were vesicle size (VS), zeta potential (ZP), and entrapment efficiency percent (EE%). The numerical optimization process resulted in an optimum formula composed of 29.645 (/%) glycerol, 0.8 (/%) cholesterol, and 5 (/%) lecithin. It showed a vesicle size of 290.4 nm, zeta potential of -34.58, and entrapment efficiency of 80.85%. The optimum formula was further characterized for DSC, XRD, TEM, in-vitro release, the effect of aging, and pharmacokinetic study. DSC thermogram confirmed the compatibility of the drug with the ingredients. XRD revealed the encapsulation of the drug in the glycerosomal nanovesicles. TEM image revealed spherical vesicles with no aggregates. Additionally, it showed enhanced drug release when compared to a drug suspension and also exhibited good stability for one month. Moreover, it showed higher brain C, AUC, and AUC and plasma AUC and AUC in comparison to drug suspension. It showed brain and plasma bioavailability enhancement of 153.15 and 179.85%, respectively, compared to the drug suspension. So, the optimum glycerosomal formula may be regarded as a promising carrier to enhance the oral bioavailability and brain delivery of Quetiapine fumarate.
本研究旨在制备富马酸喹硫平（QTF）的脂质体制剂并进行统计学优化，以提高其口服生物利用度并增强其脑内递送。该研究采用Design-Expert软件的中心复合旋转设计进行。研究中的自变量为甘油百分比/%和胆固醇百分比/%，因变量为囊泡大小（VS）、ζ电位（ZP）和包封率百分比（EE%）。数值优化过程得到了一种最佳配方，其由29.645（/%）甘油、0.8（/%）胆固醇和5（/%）卵磷脂组成。其囊泡大小为290.4 nm，ζ电位为 -34.58，包封率为80.85%。对最佳配方进一步进行了差示扫描量热法（DSC）、X射线衍射（XRD）、透射电子显微镜（TEM）、体外释放、老化影响和药代动力学研究。DSC热谱图证实了药物与成分的相容性。XRD显示药物被包裹在脂质体纳米囊泡中。TEM图像显示为无聚集的球形囊泡。此外，与药物混悬液相比，它显示出增强的药物释放，并且在一个月内也表现出良好的稳定性。此外，与药物混悬液相比，它在脑内的Cmax、AUC以及血浆中的AUC都更高。与药物混悬液相比，它在脑内和血浆中的生物利用度分别提高了153.15%和179.85%。因此，最佳脂质体配方可被视为一种有前景的载体，用于提高富马酸喹硫平的口服生物利用度和脑内递送。
