Park Young-Joon, Ryu Dong-Sung, Li Dong Xun, Quan Qi Zhe, Oh Dong Hoon, Kim Jong Oh, Seo Youn Gee, Lee Young-Im, Yong Chul Soon, Woo Jong Soo, Choi Han-Gon
Research Center, Samil Pharmaceutical Co. Ltd., Ansan 712-749, Korea.
Arch Pharm Res. 2009 Jun;32(6):893-8. doi: 10.1007/s12272-009-1611-5. Epub 2009 Jun 26.
To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.
为了开发一种具有改善溶解性的新型载他克莫司固体分散体，采用喷雾干燥技术，以不同比例的水、十二烷基硫酸钠、柠檬酸和羧甲基纤维素钠制备了各种固体分散体。使用扫描电子显微镜、差示扫描量热法和粉末X射线衍射研究了固体分散体的物理化学性质。此外，与药物粉末相比，评估了它们的溶解度和溶出度。他克莫司/羧甲基纤维素钠/十二烷基硫酸钠/柠檬酸比例为3/24/3/0.2的固体分散体与粉末相比，显著提高了药物的溶解度和溶出度。扫描电子显微镜结果表明，在这种固体分散体中载体可能附着在药物表面。与传统固体分散体系统不同，通过差示扫描量热法和粉末X射线衍射分析证实，这种固体分散体中药物的晶型不能转化为无定形形式。因此，含有水、十二烷基硫酸钠、柠檬酸和羧甲基纤维素钠的固体分散体系统应该是一种潜在的候选物，用于递送具有增强溶解度且无晶型转化的难溶性他克莫司。
