聚乙二醇-12-羟基硬脂酸酯对尼莫地平体外溶出及口服吸收的影响

发布时间：2018-05-16 22:38

  本文选题：尼莫地平 + Solutol　； 参考：《天津大学》2014年硕士论文

【摘要】：尼莫地平是治疗高血压及脑血管疾病的药物,现有的剂型有片剂和溶液型注射剂。由于尼莫地平在水中几乎不溶解,导致其口服制剂的生物利用度仅为10%~30%,因此,有必要通过制剂增溶技术来提高其水溶性。本课题采用分散技术,以新型表面活性剂聚乙二醇-12-羟基硬脂酸酯(Solutol HS-15)为载体材料,通过溶剂分散法考察了载体材料对尼莫地平的溶解度和体外溶出度的影响。结果表明,在促进药物水中溶解度的性能方面,Solutol HS-15在Solutol HS-15与尼莫地平复合物中所占的比例越高,则尼莫地平在水中的溶解度就提高越多。用药物载体材料复合物制成了片剂,Solutol HS-15对于尼莫地平的增溶效果优于传统的用聚乙二醇4000制备的固体分散体,在Solutol HS-15与尼莫地平比例为1:1时,在37℃下对药物水中的溶解度提高了7.4倍,相同用量下,Solutol HS-15对尼莫地平的增溶效果优于聚乙二醇4000。对Solutol HS-15与尼莫地平复合物制备的片剂进行了体外溶出度考察,结果表明:在水温为37℃,转速为100rpm的测试条件下,尼莫地平在人工胃液和人工肠液两种不同介质中的溶出均较未加Solutol HS-15的片剂的溶出度有明显改善,药物的体外溶出度也高于目前市售的国产片剂。以家兔为实验动物进行的口服吸收和药代动力学试验表明:加入了Solutol HS-15的片剂其体外溶出度较未加Solutol HS-15的粉末胶囊的生物利用度高出4.8倍,较市售片剂的生物利用度提高了25%。作为一种新型无毒无刺激的表面活性剂,Solutol HS-15除了可以用在注射剂中增加药物的溶解度外,也可以用在口服固体制剂中用于提高药物的体外溶出度和口服后的吸收和生物利用度。本课题的研究方法及结果对于尼莫地平口服固体制剂的开发以及其它水难溶药物口服固体制剂生物利用度的改善具有一定的参考意义。
[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，

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