Department of Pharmaceutics, National Organization for Drug Control and Research (NODCAR), 6 AbouHazem Street, Pyramids, Giza, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
AAPS PharmSciTech. 2018 Nov;19(8):3791-3808. doi: 10.1208/s12249-018-1142-9. Epub 2018 Oct 2.
Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the stomach contents reflux abnormally into the esophagus. GERD complications include esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially used to treat GERD. Yet, its low solubility and bioavailability due to extensive first-pass metabolism limits its applications. This study aimed to formulate MOS nanostructured lipid carriers (MOS-NLCs) via the intranasal route to improve its bioavailability. Melt-emulsification low temperature-solidification technique using 2 full factorial design was adopted to formulate MOS-NLCs. Eight formulae were prepared and assessed in terms of entrapment efficiency (%EE), particle size, and in vitro release. Glycerol addition significantly reduced the particle sizes and improved %EE and %drug released. Surface modification using chitosan was applied. The optimized MOS surface-modified nanostructured lipid carriers (MOS-SMNLCs-F7)(stearic acid, 4% glycerol, 0.5% LuterolF127, 0.5% chitosan) showed low particle size 413.8 nm ± 11.46 nm and high %EE 90.19% ± 0.06% and a threefold increase in permeation of MOS with respect to the drug suspension. MOS-SMNLCs (F7) was also evaluated for its bioavailability compared with drug suspension and commercial product. Statistical analysis revealed a significant increase in gastric emptying rate to be 21.54 ± 1.88 contractions/min compared with10.02 ± 0.62 contractions/min and 8.9 ± 0.72 contractions/min for drug suspension and oral marketed product respectively. Pharmacokinetic studies showed 2.44-fold rise in bioavailability as compared to MOS suspension and 4.54-fold as compared to the oral marketed product. In vitro/in vivo studies proven to level A correlation between in vitro permeation through sheep nasal mucosa and in vivo absorption. Therefore, MOS-SMNLCs could be considered a step forward towards enhancing the clinical efficacy of Mosapride.
胃食管反流病（GERD）是一种食管损伤，当胃内容物异常反流到食管时发生。GERD 的并发症包括食管腺癌。莫沙必利（MOS）是一种安全的促动力药物，可能用于治疗 GERD。然而，由于广泛的首过代谢，其溶解度和生物利用度低限制了其应用。本研究旨在通过鼻腔途径将 MOS 制成纳米结构脂质载体（MOS-NLCs），以提高其生物利用度。采用 2 因素完全实验设计的熔融乳化低温固化技术来制备 MOS-NLCs。制备了 8 种配方，并从包封效率（%EE）、粒径和体外释放等方面进行评估。甘油的加入显著降低了粒径，提高了%EE 和%药物释放。应用壳聚糖进行表面改性。优化的 MOS 表面改性纳米结构脂质载体（MOS-SMNLCs-F7）（硬脂酸、4%甘油、0.5% Lutrol F127、0.5%壳聚糖）显示出低粒径 413.8nm±11.46nm 和高%EE 90.19%±0.06%，与药物混悬剂相比，MOS 的渗透增加了 3 倍。还评估了 MOS-SMNLCs（F7）与药物混悬剂和市售产品相比的生物利用度。统计分析显示，与 10.02±0.62 次/分钟和 8.9±0.72 次/分钟的药物混悬剂和口服市售产品相比，胃排空率显著增加到 21.54±1.88 次/分钟。药代动力学研究表明，与 MOS 混悬剂相比，生物利用度提高了 2.44 倍，与口服市售产品相比，生物利用度提高了 4.54 倍。体外/体内研究证明，羊鼻黏膜体外渗透与体内吸收之间存在 A 级相关性。因此，MOS-SMNLCs 可被视为提高莫沙必利临床疗效的重要一步。
