Insys Therapeutics, 410S Benson Ln, Chandler, AZ 85224, United States.
Insys Therapeutics, 410S Benson Ln, Chandler, AZ 85224, United States.
Int J Pharm. 2019 Nov 25;571:118702. doi: 10.1016/j.ijpharm.2019.118702. Epub 2019 Oct 5.
Rizatriptan produces antimigraine activity by acting as selective agonist of 5-HT and 5-HT receptors present on intracranial and extracerebral blood vessels. Absorption from oral tablet is slow with T of approximately 1-1.5 h. A few attempts have been made to promote rapid absorption such as oral or sublingual films with limited success. The aim of our study was to develop intranasal spray formulation of rizatriptan with quick onset of action. Solubility was enhanced by a co-solvent system where we studied solubility of rizatriptan benzoate in pure solvents, binary and ternary mixtures. Binary and ternary co-solvents using ethanol, water, propylene glycol and polyethylene glycol resulted rizatriptan equivalent base solubility more than 60 mg/mL. Same co-solvents were used at different level to make nasal spray formulations and evaluated pharmacokinetics using beagle dog animal model. Nasal spray formulation containing 20% w/w ethanol exhibited highest exposure, where C (312 ng/mL) reached in 5 min and maintained higher concentration than oral dose for more than 30 min.
利扎曲普坦通过作用于颅内和颅外血管的 5-HT 和 5-HT 受体，产生抗偏头痛活性。口服片剂的吸收缓慢，T 约为 1-1.5 小时。曾尝试过一些促进快速吸收的方法，如口服或舌下膜，但效果有限。我们的研究旨在开发具有快速作用的利扎曲普坦鼻内喷雾制剂。共溶剂系统提高了溶解度，研究了苯甲酸利扎曲普坦在纯溶剂、二元和三元混合物中的溶解度。使用乙醇、水、丙二醇和聚乙二醇的二元和三元共溶剂使利扎曲普坦当量碱的溶解度超过 60mg/mL。使用不同水平的相同共溶剂来制备鼻内喷雾制剂，并使用比格犬动物模型评估药代动力学。含有 20%w/w 乙醇的鼻内喷雾制剂表现出最高的暴露量，其中 C（312ng/mL）在 5 分钟内达到，并保持高于口服剂量的浓度超过 30 分钟。
