COMBINATION OF METFORMIN AND CURCUMIN THERMOREVERSIBLE NASAL IN SITU GEL FORMULATION AND IN VITRO-EX VIVO EVALUATION FOR DIABETES-INDUCED ALZHEIMER’S DISEASE

A. Anku, K. Abbulu, S. Battu, Kalam Marryswarnalatha, T. S. Lakshmi
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Abstract

The present research was focused to prepare the formulation containing combination of Metformin and Curcumin to control diabetes-induced Alzheimer’s in elderly population with the utilization of Poloxamer P188 (8%), a thermoreversible gelling polymer, and mucoadhesive polymers such as Carbopol 940, Sodium alginate and HPMC K100 in varying concentrations (0.5%, 1%, 1.5% and 2% respectively) to improve the absorption of drugs by increasing the contact time with nasal mucosa. The in situ gel was prepared by cold method and administered via nasal route to deliver the drug directly to CNS by bypassing BBB and to improve patient compliance, nasal bioavailability of drugs by cumulative its nasal retention time in nasal mucosa. Total 12 nasal in situ gels were prepared and evaluated for in vitro studies and ex vivo drug diffusion studies (goat nasal mucosa) and results were found to be satisfactory. Moreover, histopathological studies revealed that the preparation was safe to be used on nasal mucosa of goat. The prepared nasal in situ gel is an effective alternative to conventional method and can be used to treat diabetes-induced Alzheimer’s disease.
二甲双胍和姜黄素复合热可逆鼻腔原位凝胶制剂及对糖尿病诱导的阿尔茨海默病的体外体外评价
本研究主要利用热可逆胶凝聚合物Poloxamer P188(8%)和黏附聚合物Carbopol 940、海藻酸钠、HPMC K100等不同浓度(分别为0.5%、1%、1.5%和2%),通过增加与鼻黏膜的接触时间来提高药物的吸收,制备二甲双胍与姜黄素联用治疗老年糖尿病性阿尔茨海默氏症的配方。采用冷法制备原位凝胶,经鼻经血脑屏障直接给药至中枢神经系统,通过累积药物在鼻黏膜的鼻滞留时间,提高药物的依从性和鼻生物利用度。共制备了12种鼻腔原位凝胶,并对其进行了体外研究和离体药物扩散研究(山羊鼻粘膜),结果令人满意。组织病理学研究表明,该制剂用于山羊鼻黏膜是安全的。所制备的鼻腔原位凝胶是常规方法的有效替代,可用于治疗糖尿病性阿尔茨海默病。
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