亚临界水法制备丙酸倍氯米松纳米颗粒及其溶解度的研究

发布时间：2018-06-22 18:50

  本文选题：亚临界水 + 纳米颗粒　； 参考：《北京化工大学》2015年硕士论文

【摘要】：在药物制剂中绝大多数的药物是水难溶性药物,由于该类药在水中溶解度小,溶出速率慢使得水难溶性药物很难被人体吸收,降低了其生物利用度。改善水难溶性药物的溶出速率得到了广泛的关注,研究发现具有良好尺寸的药物颗粒,其溶出速率会明显增大。因此,通过不同的制备方法使药物颗粒的尺寸减小、粒径分布变窄从而提高药物的生物利用度。介质研磨法是一种非常普遍的制备纳米药物颗粒的方法,但是在研磨过程中,高能量消耗、污染药物、产物颗粒粒径分布宽等阻碍了这一技术的发展。相比于传统方法,亚临界水法制备纳米颗粒具有无毒、绿色等优势。亚临界水是处于临界压力下呈流体状态的加压热水,在此状态下可以与非极性有机溶剂产生互溶。通过提高亚临界水温度来改变水的极性,使得亚临界水具有溶解非极性有机物的特性。本文通过研究丙酸倍氯米松在亚临界水中的溶解度数据,建立合适的溶解度模型,并研究了亚临界水溶剂-反溶剂法对丙酸倍氯米松颗粒制备工艺的影响。首先研究了平衡时间对丙酸倍氯米松在亚临界水中的影响,发现亚临界水温度从120℃升高到160℃的过程中,药物在亚临界水中的溶解平衡时间延长,确定20min为溶解平衡时间。其次,考察了压力的变化对丙酸倍氯米松的溶解度的影响,结果表明6MPa和8MPa压力下的丙酸倍氯米松的溶解度变化很小。最后,考察了温度和共剂含量对丙酸倍氯米松溶解度的影响,结果表明丙酸倍氯米松在亚临界水中的溶解度随着温度的升高而增大,在150℃以后,溶解度上升速度加快。当乙醇加入到亚临界水体系中使丙酸倍氯米松的溶解度增大为原溶解度的10倍以上。通过亚临界水技术制备丙酸倍氯米松纳米颗粒,研究了反溶剂的温度、亚临界水的温度、亚临界水/反溶剂的体积比、表面活性剂的种类、不同PEG和PVP的含量对丙酸倍氯米松纳米颗粒形貌的影响,选择反溶剂温度为0℃、亚临界水温度为140℃、亚临界水/反溶剂体积比为1:3、PEG和PVP含量为0.018%为实验最优条件,在此条件下制备出粒径小于60nm的丙酸倍氯米松药物颗粒。FT-IR结果表明丙酸倍氯米松经过亚临界水处理后化学结构没有发生改变,XRD结果表明药物纳米颗粒的衍射峰强度减弱,这是由于亚临界水过程使药物颗粒的粒径减小,降低了药物颗粒结晶度。体外溶出速率分析结果表明丙酸倍氯米松原料药在120min后只溶出了10.78%,然而经过亚临界水法制备的丙酸倍氯米松纳米颗粒在120min后溶出60.13%。
[Abstract]:The majority of drugs in pharmaceutical preparations are water-insoluble drugs. Because of their low solubility in water and slow dissolution rate, water-insoluble drugs are difficult to be absorbed by human body, and the bioavailability of water-insoluble drugs is reduced. To improve the dissolution rate of water-insoluble drugs has been widely concerned. It has been found that the dissolution rate of drug particles with good size will increase significantly. Therefore, different preparation methods can reduce the size of drug particles and narrow the particle size distribution so as to improve the bioavailability of drugs. Medium grinding is a very common method for preparing nanoparticles. However, the development of this technology is hindered by high energy consumption, contaminated drugs and wide particle size distribution in the grinding process. Compared with the traditional method, the preparation of nanoparticles by subcritical water method has the advantages of nontoxic and green. Subcritical water is a pressurized hot water in a fluid state at critical pressure, in which it can be dissolved with non-polar organic solvents. By increasing the temperature of the subcritical water, the polarity of the water is changed, which makes the subcritical water have the property of dissolving non-polar organic matter. By studying the solubility data of beclomethasone propionate in subcritical water, a suitable solubility model was established, and the effect of subcritical water solvent-antisolvent method on the preparation process of beclomethasone propionate granules was studied. The effect of equilibrium time on the dissolution of beclomethasone propionate in subcritical water was studied. It was found that when the temperature of subcritical water increased from 120 鈩，

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