盐酸纳洛酮鼻腔喷雾剂的制备及评价  

Preparation and evaluation of naloxone hydrochloride nasal spray

作　　者：杨鹏[1,2] 李琬晴 李迎[2] 孙建绪[2] 张慧[2] 高静[2] 印晓星 郑爱萍[1,2] YANG Peng LI Wan-qing LI Ying SUN Jian-xu ZHANG Hui GAO Jing YIN Xiao-xing ZHENG Ai-ping(Xuzhou Medical University, Xuzhou 221004, China State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China School of Preclinical Medicine, Beijing University of Traditional Chinese Medicine, Beijing 100029, China)

机构地区：[1]徐州医科大学,徐州221004 [2]军事医学科学院毒物药物研究所药物制剂室抗毒药物与毒理学国家重点实验室,北京100850 [3]北京中医药大学基础医学院,北京100029

出　　处：《国际药学研究杂志》2017年第6期616-621,共6页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金资助项目(81573357);北京市自然科学基金资助项目(7162148)

摘　　要：目的制备盐酸纳洛酮鼻腔喷雾剂并考察制剂的纤毛毒性和体内药代动力学行为。方法考察盐酸纳洛酮在不同pH溶液中的稳定性,不同吸收促进剂对盐酸纳洛酮的促渗透效果,筛选出适宜的处方;以离体蟾蜍上颚黏膜表面纤毛的相对运动百分率评价盐酸纳洛酮鼻腔喷雾剂的纤毛毒性;考察盐酸纳洛酮鼻腔喷雾剂在大鼠体内的药代动力学行为。结果盐酸纳洛酮溶液在pH3.5~5.5范围内稳定,0.2%乙二胺四乙酸二钠(EDTA-2Na)促渗透效果最好;盐酸纳洛酮鼻腔喷雾剂的纤毛毒性小且可恢复;盐酸纳洛酮鼻腔喷雾剂起效快,在大鼠体内的生物利用度与肌肉注射相当。结论本文制备的鼻腔喷雾剂体外性质稳定可控,纤毛毒性小,起效快,生物利用度高,具有较好的应用前景。Objective To prepare naloxone hydrochloride nasal spray and evaluate the ciliotoxicity and pharmacokinetics of the formulation. Methods The stability of naloxone hydrochloride was studied in pH3.5-5.5. Penetration promoting effects of absorption enhancers on the naloxone hydrochloride were evaluated. Nasal ciliotoxicity studies were carried out using isolated toad palate.Rats were treated with naloxone hydrochloride solution by intramuscular injection of nasal drops to evaluate the pharmacokinetics.Results Naloxone hydrochloride solution was stable in pH3.5-5.5. Disodium ethylenediaminetetraacetic acid（0.2%,W/V）had the best penetration promoting effect on naloxone hydrochloride. Naloxone hydrochloride nasal spray did not exhibit obvious nasal ciliotoxicity compared to the negative control. The nasal spray had a faster therapeutic effect and its bioavailability was similar to that of the intramuscular injection. Conclusion Naloxone hydrochloride nasal spray prepared in this research is stable with no obvious nasal ciliotoxicity,has faster therapeutic effect,and good bioavailability,so may have a broad application prospect.

关 键 词：盐酸纳洛酮 鼻腔喷雾剂 吸收促进剂 纤毛毒性 药代动力学 

分 类 号：R943[医药卫生—药剂学]