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通过将药物在亲水性溶剂中的溶液吸附到高表面积载体上提高难溶性药物的溶出速率。

Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs in hydrophilic solvents onto high surface area carriers.

作者信息

Friedrich Heike, Fussnegger Bernd, Kolter Karl, Bodmeier Roland

机构信息

College of Pharmacy, Freie Universität Berlin, Berlin, Germany.

出版信息

Eur J Pharm Biopharm. 2006 Feb;62(2):171-7. doi: 10.1016/j.ejpb.2005.08.013. Epub 2005 Nov 4.

Abstract

The dissolution rate of the model drugs carbamazepine and nifedipine was improved by adsorbing solutions of the drugs in hydrophilic non-volatile or volatile solvents onto carriers with a large surface area. This was accomplished by dissolving the drug in methanol or the non-toxic hydrophilic liquids PEG 400 or 2-pyrrolidone, and adsorbing these solutions onto the surface of silica (Aerosil) or crosslinked polyvinylpyrrolidone (Kollidon CL-M). The solvent binding capacities decreased in the order of methanol, PEG 400, 2-pyrrolidone for Aerosil 200, 300, 380 and for Kollidon CL-M. Kollidon bound less liquid than Aerosil because of the smaller surface area. Differential scanning calorimetry measurements showed higher interactions between drugs and Kollidon compared to Aerosil, suggesting a low aggregation of precipitated drug particles. The drug release from the adsorbent systems was enhanced when compared to micronized drug and independent of the drug loading in the investigated range. The drugs were also dissolved in various liquid, paste-like or solid solubilisers (polyoxyl-40-hydrogenated castor oil (Cremophor RH 40), macrogol-15-hydroxystearate (Solutol HS), poloxamers (Lutrol F68, Pluronic F87NF and Pluronic L44NF) and adsorbed onto Kollidon. These adsorbent systems also exhibited an increased dissolution rate when compared to pure drug.

摘要

通过将卡马西平和硝苯地平这两种模型药物溶解于亲水性非挥发性或挥发性溶剂中,再将溶液吸附到具有大表面积的载体上,可提高药物的溶出速率。具体做法是将药物溶解于甲醇或无毒亲水性液体聚乙二醇400(PEG 400)或2-吡咯烷酮中,然后将这些溶液吸附到二氧化硅(气相法二氧化硅)或交联聚乙烯吡咯烷酮(交联聚维酮,Kollidon CL-M)的表面。对于气相法二氧化硅200、300、380以及交联聚维酮,按甲醇、PEG 400、2-吡咯烷酮的顺序,溶剂结合能力逐渐降低。由于表面积较小,交联聚维酮结合的液体比气相法二氧化硅少。差示扫描量热法测量结果表明,与气相法二氧化硅相比,药物与交联聚维酮之间的相互作用更强,这表明沉淀的药物颗粒聚集程度较低。与微粉化药物相比,吸附剂系统的药物释放得到增强,且在所研究的范围内与药物载量无关。药物还可溶解于各种液体、膏状或固体增溶剂(聚氧乙烯40氢化蓖麻油(克列莫佛RH 40)、聚乙二醇15羟基硬脂酸酯(Solutol HS)、泊洛沙姆(路路通F68、普朗尼克F87NF和普朗尼克L44NF))中,然后吸附到交联聚维酮上。与纯药物相比,这些吸附剂系统的溶出速率也有所提高。

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