發(fā)布時間：2018-06-22 18:50

  本文選題：亞臨界水 + 納米顆粒��； 參考：《北京化工大學(xué)》2015年碩士論文

【摘要】：在藥物制劑中絕大多數(shù)的藥物是水難溶性藥物,由于該類藥在水中溶解度小,溶出速率慢使得水難溶性藥物很難被人體吸收,降低了其生物利用度。改善水難溶性藥物的溶出速率得到了廣泛的關(guān)注,研究發(fā)現(xiàn)具有良好尺寸的藥物顆粒,其溶出速率會明顯增大。因此,通過不同的制備方法使藥物顆粒的尺寸減小、粒徑分布變窄從而提高藥物的生物利用度。介質(zhì)研磨法是一種非常普遍的制備納米藥物顆粒的方法,但是在研磨過程中,高能量消耗、污染藥物、產(chǎn)物顆粒粒徑分布寬等阻礙了這一技術(shù)的發(fā)展。相比于傳統(tǒng)方法,亞臨界水法制備納米顆粒具有無毒、綠色等優(yōu)勢。亞臨界水是處于臨界壓力下呈流體狀態(tài)的加壓熱水,在此狀態(tài)下可以與非極性有機溶劑產(chǎn)生互溶。通過提高亞臨界水溫度來改變水的極性,使得亞臨界水具有溶解非極性有機物的特性。本文通過研究丙酸倍氯米松在亞臨界水中的溶解度數(shù)據(jù),建立合適的溶解度模型,并研究了亞臨界水溶劑-反溶劑法對丙酸倍氯米松顆粒制備工藝的影響。首先研究了平衡時間對丙酸倍氯米松在亞臨界水中的影響,發(fā)現(xiàn)亞臨界水溫度從120℃升高到160℃的過程中,藥物在亞臨界水中的溶解平衡時間延長,確定20min為溶解平衡時間。其次,考察了壓力的變化對丙酸倍氯米松的溶解度的影響,結(jié)果表明6MPa和8MPa壓力下的丙酸倍氯米松的溶解度變化很小。最后,考察了溫度和共劑含量對丙酸倍氯米松溶解度的影響,結(jié)果表明丙酸倍氯米松在亞臨界水中的溶解度隨著溫度的升高而增大,在150℃以后,溶解度上升速度加快。當(dāng)乙醇加入到亞臨界水體系中使丙酸倍氯米松的溶解度增大為原溶解度的10倍以上。通過亞臨界水技術(shù)制備丙酸倍氯米松納米顆粒,研究了反溶劑的溫度、亞臨界水的溫度、亞臨界水/反溶劑的體積比、表面活性劑的種類、不同PEG和PVP的含量對丙酸倍氯米松納米顆粒形貌的影響,選擇反溶劑溫度為0℃、亞臨界水溫度為140℃、亞臨界水/反溶劑體積比為1:3、PEG和PVP含量為0.018%為實驗最優(yōu)條件,在此條件下制備出粒徑小于60nm的丙酸倍氯米松藥物顆粒。FT-IR結(jié)果表明丙酸倍氯米松經(jīng)過亞臨界水處理后化學(xué)結(jié)構(gòu)沒有發(fā)生改變,XRD結(jié)果表明藥物納米顆粒的衍射峰強度減弱,這是由于亞臨界水過程使藥物顆粒的粒徑減小,降低了藥物顆粒結(jié)晶度。體外溶出速率分析結(jié)果表明丙酸倍氯米松原料藥在120min后只溶出了10.78%,然而經(jīng)過亞臨界水法制備的丙酸倍氯米松納米顆粒在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，

本文編號：2053854