Rizatriptan produces antimigraine activity by acting as selective agonist of 5-HT1B and 5-HT1D receptors present on intracranial and extracerebral blood vessels. Absorption from oral tablet is slow with Tmax of approximately 1-1.5 hours. 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 Cmax (312 ng/mL) reached in 5 minutes and maintained higher concentration than oral dose for more than 30 minutes.

中文翻译：

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含有利扎曲普坦苯甲酸酯的鼻内喷雾剂治疗偏头痛

利扎曲普坦通过充当颅内和脑外血管上存在的5-HT1B和5-HT1D受体的选择性激动剂来产生抗偏头痛活性。口服片剂吸收缓慢，Tmax约为1-1.5小时。已经进行了一些尝试来促进快速吸收，例如口服或舌下膜，但效果有限。我们研究的目的是开发起效迅速的利扎曲普坦鼻内喷雾剂。通过共溶剂系统提高了溶解度，我们在其中研究了利扎曲普坦苯甲酸酯在纯溶剂，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助溶剂可产生的利扎曲普坦当量碱溶解度超过60 mg / mL。使用相同的助溶剂以不同的水平制备鼻喷雾剂，并使用比格犬动物模型评估其药代动力学。含有20％w / w乙醇的鼻喷雾制剂显示出最高的暴露水平，其中Cmax（312 ng / mL）在5分钟内达到最高浓度，并且在30分钟内保持高于口服剂量的浓度。