發(fā)布時(shí)間：2018-05-16 22:38

  本文選題：尼莫地平 + Solutol　； 參考：《天津大學(xué)》2014年碩士論文

【摘要】：尼莫地平是治療高血壓及腦血管疾病的藥物,現(xiàn)有的劑型有片劑和溶液型注射劑。由于尼莫地平在水中幾乎不溶解,導(dǎo)致其口服制劑的生物利用度僅為10%~30%,因此,有必要通過制劑增溶技術(shù)來提高其水溶性。本課題采用分散技術(shù),以新型表面活性劑聚乙二醇-12-羥基硬脂酸酯(Solutol HS-15)為載體材料,通過溶劑分散法考察了載體材料對(duì)尼莫地平的溶解度和體外溶出度的影響。結(jié)果表明,在促進(jìn)藥物水中溶解度的性能方面,Solutol HS-15在Solutol HS-15與尼莫地平復(fù)合物中所占的比例越高,則尼莫地平在水中的溶解度就提高越多。用藥物載體材料復(fù)合物制成了片劑,Solutol HS-15對(duì)于尼莫地平的增溶效果優(yōu)于傳統(tǒng)的用聚乙二醇4000制備的固體分散體,在Solutol HS-15與尼莫地平比例為1:1時(shí),在37℃下對(duì)藥物水中的溶解度提高了7.4倍,相同用量下,Solutol HS-15對(duì)尼莫地平的增溶效果優(yōu)于聚乙二醇4000。對(duì)Solutol HS-15與尼莫地平復(fù)合物制備的片劑進(jìn)行了體外溶出度考察,結(jié)果表明:在水溫為37℃,轉(zhuǎn)速為100rpm的測(cè)試條件下,尼莫地平在人工胃液和人工腸液兩種不同介質(zhì)中的溶出均較未加Solutol HS-15的片劑的溶出度有明顯改善,藥物的體外溶出度也高于目前市售的國產(chǎn)片劑。以家兔為實(shí)驗(yàn)動(dòng)物進(jìn)行的口服吸收和藥代動(dòng)力學(xué)試驗(yàn)表明:加入了Solutol HS-15的片劑其體外溶出度較未加Solutol HS-15的粉末膠囊的生物利用度高出4.8倍,較市售片劑的生物利用度提高了25%。作為一種新型無毒無刺激的表面活性劑,Solutol HS-15除了可以用在注射劑中增加藥物的溶解度外,也可以用在口服固體制劑中用于提高藥物的體外溶出度和口服后的吸收和生物利用度。本課題的研究方法及結(jié)果對(duì)于尼莫地平口服固體制劑的開發(fā)以及其它水難溶藥物口服固體制劑生物利用度的改善具有一定的參考意義。
[Abstract]:Nimodipine is a drug for the treatment of hypertension and cerebrovascular diseases. Because Nimodipine is almost insoluble in water, the bioavailability of its oral preparation is only 10% and 30%. Therefore, it is necessary to improve the water solubility of Nimodipine by means of solubilization technology. In this paper, a new surfactant, poly (ethylene glycol) -12-hydroxystearate (Solutol HS-15), was used as the carrier material. The influence of the carrier material on the solubility and dissolution of nimodipine in vitro was investigated by solvent dispersion method. The results showed that the higher the proportion of Solutol HS-15 in the complex of Solutol HS-15 and nimodipine, the higher the solubility of nimodipine in water. The solubilization effect of Solutol HS-15 on nimodipine was better than that of the traditional solid dispersion prepared with polyethylene glycol 4000. When the ratio of Solutol HS-15 to nimodipine was 1:1, The solubility of Nimodipine in water was increased by 7.4 times at 37 鈩，

本文編號(hào)：1898737