El-Setouhy Doaa Ahmed, Ahmed Sami, Badawi Alia Abd El-Latif, El-Nabarawi Mohamed Ahmed, Sallam Nada
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Eur J Pharm Sci. 2015 Aug 30;76:48-56. doi: 10.1016/j.ejps.2015.04.015. Epub 2015 Apr 25.
Granisetron hydrochloride is a potent antiemetic yet experiencing first pass metabolism. Ketorolac tromethamine is a potent analgesic NSAID that is known to cause gastrointestinal complications. The purpose of this study is to prepare combined in situ nasal copolymer thermal gel combining both drugs for the management of postoperative and cancer associated nausea, vomiting and pain while avoiding the problems associated with their therapy. In situ gelling nasal formulations with/without different mucoadhesive polymers were prepared and evaluated. Viscosity of different formulations was measured and correlated to in-vitro drug release. Selected formulae were evaluated for in-vivo mucociliary transit time. Based on in-vitro release pattern and mucociliary transit time, the selected formula F4 was evaluated for chemical and thermal anti-nociception activity in rats following intranasal or intraperitoneal administration. Only the intra-nasal administration of the selected formulation F4 showed significant analgesia against chemical nociception during both the early and late phases. Also, intranasal administration of the selected formulation F4 showed significant analgesia against thermal nociception. F4 intranasal formulation may offer higher therapeutic value than oral administration as it may not only avoid granisetron first pass metabolism but may also minimize ketorolac gastrointestinal adverse effects as well.
盐酸格拉司琼是一种强效止吐药，但会经历首过代谢。酮咯酸氨丁三醇是一种强效镇痛非甾体抗炎药，已知会引起胃肠道并发症。本研究的目的是制备一种联合原位鼻腔共聚物热凝胶，将两种药物结合起来，用于治疗术后和癌症相关的恶心、呕吐和疼痛，同时避免与它们的治疗相关的问题。制备并评估了含有/不含有不同粘膜粘附聚合物的原位凝胶鼻腔制剂。测量了不同制剂的粘度，并将其与体外药物释放相关联。对选定的配方进行了体内粘液纤毛转运时间的评估。根据体外释放模式和粘液纤毛转运时间，对选定的配方F4在大鼠鼻腔或腹腔给药后进行化学和热抗伤害感受活性评估。仅选定配方F4的鼻腔给药在早期和晚期均显示出对化学伤害感受的显著镇痛作用。此外，选定配方F4的鼻腔给药对热伤害感受也显示出显著的镇痛作用。F4鼻腔制剂可能比口服给药具有更高的治疗价值，因为它不仅可以避免格拉司琼的首过代谢，还可以将酮咯酸的胃肠道不良反应降至最低。
