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采用声致沉淀技术制备克拉霉素水纳米混悬液以增强其溶出度

Clarithromycin dissolution enhancement by preparation of aqueous nanosuspensions using sonoprecipitation technique.

作者信息

Esfandi Es ׳hagh, Ramezani Vahid, Vatanara Alireza, Rouholamini Najafabadi Abdolhossein, Hadipour Moghaddam Seyyed Pouya

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. ; Department of Pharmaceutics, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

Iran J Pharm Res. 2014 Summer;13(3):809-18.

Abstract

Clarithromycin (CLM) is a member of macrolide family with broad spectrum antibiotic activity. It is practically insoluble in water and its poor solubility is pH dependent. In this study, series of nanosuspensions containing CLM and stabilizer such as HPMC, NaCMC, polysorbate 80, poloxamer 188 and polyvinyl alcohol in various ratios were prepared using sonoprecipitation method. Briefly, CLM was dissolved in acid solution and the pH of solution was raised under sonication and the effects of different stabilizers on particle size of nanoparticles were evaluated. Characterization of nanoparticles in terms of size, polydispersity index, zeta potential, differential scanning calorimetery and dissolution studies was performed. Antimicrobial activity of CLM nanosuspension was compared with coarse powder by using an agar well diffusion method. The results showed that HPMC was more efficient in size reduction of particles and presence of HPMC E5 with ratio of 3:5 to CLM in formulation led to develop the stable nanosuspension with particle size of 340 nm. The obtained nanosuspension successfully showed enhanced dissolution rate and antimicrobial activity.

摘要

克拉霉素(CLM)是大环内酯类家族的一员,具有广谱抗生素活性。它几乎不溶于水,其低溶解度取决于pH值。在本研究中,采用声致沉淀法制备了一系列含有CLM和稳定剂(如羟丙基甲基纤维素(HPMC)、羧甲基纤维素钠(NaCMC)、聚山梨酯80、泊洛沙姆188和聚乙烯醇)的纳米混悬液,比例各不相同。简而言之,将CLM溶解在酸性溶液中,在超声处理下提高溶液的pH值,并评估不同稳定剂对纳米颗粒粒径的影响。对纳米颗粒进行了粒径、多分散指数、zeta电位、差示扫描量热法和溶出度研究等表征。采用琼脂孔扩散法比较了CLM纳米混悬液与粗粉的抗菌活性。结果表明,HPMC在减小颗粒尺寸方面更有效,制剂中HPMC E5与CLM的比例为3:5时,可形成粒径为340 nm的稳定纳米混悬液。所得到的纳米混悬液成功地显示出提高的溶出速率和抗菌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d2d/4177641/7d4a820a3b4a/ijpr-13-809-g001.jpg

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