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摘要：目的 对阿托伐他汀进行处方前研究。方法 建立HPLC测定阿托伐他汀钙含量的方法，采用Diamonsil® C8色谱柱（250×4.6mm ，5μm）；流动相：缓冲液 3.9g/L乙酸铵溶液，用冰醋酸调PH在5.0±0.1；流动相A：乙腈，四氢呋喃与缓冲液（21:12:67）；流动相B：乙腈，四氢呋喃与缓冲液（61:12:27）；检测波长为241nm，流速为1.5mL/min，柱温35℃，进样量20uL。结果 阿托伐他汀钙在1~250ug/mL范围内，有良好的线性，精密度、稳定性、重现性良好，平均回收率为100.02%；在pH为1~7之间的溶解度随着pH的增大逐渐增大；在酸性环境中，亲脂性较强；碱性环境中，亲脂性较差。结论 建立的分析方法学可靠，处方前研究表明阿托伐他汀的溶解度随溶液pH的增加而增大，在酸性环境中亲脂性较强。 21789
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毕业论文关键词：阿托伐他汀；处方前研究；高效液相色谱法；表观溶解度；表观油水分配系数；
Preformulation Study on Atorvastatin
Abstract: Objective: to study the prescription of atorvastatin drugs, screened the new chemical entities from the perspective of excellent biological pharmacy. Methods: to establish the HPLC determination of atorvastatin calcium content, using the Diamonsil® C8 chromatographic column (250 × 4.6mm, 5 μ m); mobile phase: buffer 3.9g/L ammonium acetate solution with glacial acetic acid, regulating PH at 5 ± 0.1; mobile phase A: acetonitrile, tetrahydrofuran and buffer solution (21:12:67); the mobile phase B: acetonitrile, tetrahydrofuran and buffer solution (61:12:27); the detection wavelength was 241nm, the flow rate was 1.5mL/min, the column temperature was 35 ℃, amount of sample 20uL. Results: in the 1~250ug/mL range, atorvastatin calcium has good linearity, precision, stability, good reproducibility, the average recovery rate was 100.02%; in pH between 1~7, solubility increased gradually with the increase of pH; in the acidic environment, the more lipophilic; alkaline environment, poor lipophilicity. Conclusion: the established method is reliable, preformulation study indicated that the solubility of atorvastatin increased with increasing solution pH, in the acidic environment of the more lipophilic.
Keywords: Atorvastatin; preformulation; high performance liquid chromatography; apparent solubility; apparent partition coefficient;
目录
1前言 1
1.1立项依据 1
1.2处方前研究的必要性 2
2文献综述 3
2.1阿托伐他汀钙简介 3
2.2外观性状 4
2.3作用机理 4
2.3.1 阿托伐他汀的降脂作用 4
2.3.2 阿托伐他汀的非降脂作用 5
2.4阿托伐他汀的药代动力学和药效学 7
2.5阿托伐他汀的不良反应及使用注意事项 8
3 HPLC测定阿托伐他汀钙含量的方法学研究 9
3.1仪器与试药 9
3.1.1试药 9
3.1.2仪器 9
3.2检测波长的确定 9
3.3液相色谱分离模式的选择 10
3.4色谱条件 10
3.5系统适应性试验 11
3.6线性试验 13
3.7精密度试验 14
3.8样品溶液的稳定性考察 14
3.9重现性试验 15
3.10回收率试验 15
3.11讨论 16
4处方前研究 17
4.1 试剂与仪器 17
4.2表观溶解度的测定 17
4.2.1溶液的配制 17
4.2.2测定方法 18
4.2.3 讨论 19
4.3表观油水分配系数 19