Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs
Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs
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DOI：
10.1208/s12249-015-0381-2
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发表时间：
2015-12-01
影响因子：
3.3
通讯作者：
Ali, Raisuddin
中科院分区：
文献类型：
--
作者：
Alam, Mohd Aftab;Al-Jenoobi, Fahad I.;Ali, Raisuddin
采用助溶固体分散技术（EASD）对5种难溶性药物进行了增溶研究。采用改进的熔融法制备EASD。使药物和亲水性载体熔融，在该熔融混合物中，通过添加由有机酸（柠檬酸）和碳酸碱（碳酸氢钠）构成的荧光偶来产生荧光。使用摇瓶法在25 ° C下测定药物粉末、固体分散体和EASD的溶解度。使用分光光度计分别在246、280、260、230和232 nm（λ（max））处估计阿托伐他汀钙、头孢呋辛酯、克霉唑、酮康唑和苯甲酸甲硝唑。阿托伐他汀钙的溶解度（100 - 345 μ g/ml），头孢呋辛酯（从441到1948 μ g/ml），克霉唑（63至677 μ g/ml），酮康唑甲硝唑苯甲酸盐（从112 μ g/ml到208 μ g/ml）对EASD的作用分别增强了3.45、4.4、10.7、31.2和1.8倍。比较了药物粉末、固体分散体和EASD的扫描电子显微镜照片。EASD的扫描电子显微照片显示药物颗粒在载体基质中均匀分布。头孢呋辛酯颗粒的形态（大小和形状）在固体分散体中以及在EASD中发生改变。EASD显示出比常规固体分散体更好的溶解度增强。本技术更适合于具有低熔点或熔化而不炭化的药物。泡腾辅助熔融技术制备固体分散体可用于提高难溶性药物的溶解度、溶出度和生物利用度。
The solubility of five poorly soluble drugs was enhanced by using an effervescence assisted solid dispersion (EASD) technique. EASDs were prepared by using modified fusion method. Drug and hydrophilic carrier were melted, and in this molten mixture, effervescence was generated by adding effervescence couple comprising organic acid (citric acid) and carbonic base (sodium bicarbonate). Solubility of drug powders, solid dispersions, and EASDs was determined at 25 degrees C using shake flask method. Atorvastatin calcium, cefuroxime axetil, clotrimazole, ketoconazole, and metronidazole benzoate were estimated using a spectrophotometer at 246, 280, 260, 230, and 232 nm (lambda(max)), respectively. Solubility of atorvastatin calcium (from 100 to 345 mu g/ml), cefuroxime axetil (from 441 to 1948 mu g/ml), clotrimazole (from 63 to 677 mu g/ml), ketoconazole (from 16 to 500 mu g/ml), and metronidazole benzoate (from 112 to 208 mu g/ml) in EASDs was enhanced by 3.45-, 4.4-, 10.7-, 31.2-, and 1.8-fold, respectively. Scanning electron micrographs of drug powder, solid dispersion, and EASDs were compared. Scanning electron micrographs of EASDs showed a uniform distribution of drug particles in the carrier matrix. Morphology (size and shape) of cefuroxime axetil particles was altered in solid dispersion as well as in EASD. EASDs showed better solubility enhancement than conventional solid dispersions. The present technique is better suitable for drugs having a low melting point or melt without charring. Effervescence assisted fusion technique of preparing solid dispersions can be employed for enhancing solubility, dissolution, and bioavailability of poorly soluble drugs.