Ali Ahmed Mahmoud Abdelhaleem, Al-Remawi Mayyas Mohammad Ahmad
Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, Taif, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, Taif, Saudi Arabia; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan.
J Pharm (Cairo). 2016;2016:2126056. doi: 10.1155/2016/2126056. Epub 2016 Nov 30.
Improving the physicochemical properties and oral bioavailability of quetiapine fumarate (QF) enabling enhanced antipsychotic attributes are the main aims of this research. The freeze dried solid dispersion strategy was adopted using nicotinamide (NIC) as highly soluble coformer. The prepared dispersions were characterized using scanning electron microscopy (SEM) differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Static disc intrinsic dissolution rate and ex vivo diffusion through intestinal tissues were conducted and compared to pure quetiapine fumarate. The results demonstrated a highly soluble coamorphous system formed between quetiapine fumarate and nicotinamide at 1 : 3 molar ratio through H-bonding interactions. The results showed >14-fold increase in solubility of QF from the prepared dispersions. Increased intrinsic dissolution rate (from 0.28 to 0.603 mg cm min) and faster flux rate through duodenum (from 0.027 to 0.041 mg cm h) and jejunum (0.027 to 0.036 mg cm h) were obtained. The prepared coamorphous dispersion proved to be effective in improving the drug solubility and dissolution rate and ex vivo diffusion. Therefore, binary coamorphous dispersions could be a promising solution to modify the physicochemical properties, raise oral bioavailability, and change the biopharmaceutics classification (BCS) of some active pharmaceutical ingredients.
改善富马酸喹硫平（QF）的物理化学性质和口服生物利用度以增强抗精神病特性是本研究的主要目标。采用冷冻干燥固体分散策略，使用烟酰胺（NIC）作为高溶性共形成剂。使用扫描电子显微镜（SEM）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）和X射线衍射（XRD）对制备的分散体进行表征。进行了静态圆盘固有溶解速率和通过肠组织的体外扩散实验，并与纯富马酸喹硫平进行比较。结果表明，富马酸喹硫平和烟酰胺以1:3摩尔比通过氢键相互作用形成了高溶性共无定形体系。结果显示，制备的分散体使QF的溶解度提高了14倍以上。固有溶解速率增加（从0.28提高到0.603 mg cm min），通过十二指肠的通量速率加快（从0.027提高到0.041 mg cm h），空肠的通量速率也加快（从0.027提高到0.036 mg cm h）。制备的共无定形分散体被证明在提高药物溶解度、溶解速率和体外扩散方面是有效的。因此，二元共无定形分散体可能是一种有前景的解决方案，可用于改变某些活性药物成分的物理化学性质、提高口服生物利用度并改变生物药剂学分类（BCS）。
