佐米曲坦缓释及速释固体分散体的制备工艺研究.docVIP

佐米曲坦缓释及速释固体分散体的制备工艺研究 　　[摘要] 目的 制备佐米曲坦缓释和速释固体分散体，提高佐米曲坦生物利用度。 方法 采用固体分散体技术，制备佐米曲坦缓释及速释固体分散体，考察载体种类、用量等对体外释放度的影响。 结果 缓释固体分散体受乙基纤维素（EC）黏度、释放调节剂PEG6000用量、药物与载体用量比例的影响。选择EC（10 cP）和聚乙二醇（PEG）6000混合物为载体材料，其中PEG6000占混合载体总量的40%，控制药物与载体材料比为1∶4，缓释效果较好。采用药物、PEG6000与泊洛沙姆188比例为1∶3.7∶1制备速释固体分散体，药物溶出速率显著提高。 结论 缓释及速释固体分散体能提高药物溶出量，处方合理，具有良好的缓释效果。 　　[关键词] 佐米曲坦；固体分散体；缓释；速释 　　[中图分类号] R944.2 [文献标识码] A [文章编号] 1673-7210（2017）01（a）-0016-04 　　[Abstract] Objective To prepare Zolmitriptan sustained-release and immediate-release solid dispersions （SD） and improve bioavailability. Methods SD technology was used to prepare immediate-release and sustained release SD of Zolmitriptan， the effect of the preparing technology on the in vitro release with the type and quality of carrier material was examined. Results The viscosity of ethyl cellulose （EC） and the dosage of PEG6000 releasing moderator， and the ratio of drug and carrier could impact on the release rates in vitro. When the mixture of EC（10 cP） and PEG6000 as a carrier material to Zolmitriptan was 4∶1， and 40% of the mixed carrier as PEG6000， the sustained-release effect was satisfactory. The dissolution rate were improved significantly to the fast released solid dispersion by using drugs and PEG6000 and poloxamer 188 with a ratio of 1∶3.7∶1. Conclusion The immediate-release and sustained release SD can increase the amount of drug dissolution， the fomulation is reasonable， and the SD using EC and PEG6000 as the carrier has good and stable sustained-release effect. 　　[Key words] Zolmitriptan； Solid dispersion； Sustained-release； Immediate-release 　　佐米曲坦（Zolmitriptan）作为二代曲坦类的典型药物，对于偏头痛的治疗具有良好的效果。偏头痛的发作基本为外周和中枢神经血管被激活，引发级联式神经源性炎症[1]。由于神经或血管性功能失调等原因引起偏头痛类疾病，普遍为一侧头部疼痛发作，间或有双侧头部疼痛反复发作等特点[2-3]。曲坦类药物具有良好选择性和强效血清素5-HT1B/1D[4]，佐米曲坦通过口服吸收迅速和完全，血浆浓度可以维持4～6 h。其药代动力学呈线性关系的剂量范围为2.5～50 mg，约2.5 h的消除半衰期，生物利用度大约为40%，佐米曲坦和它的代谢物与血浆蛋白结合率较低[5]，约为25%。在售药品药物近40%属于难溶性药品，而在研药物中难溶性药物比例更高[6]。由于溶解性的限制，一些具有药理活性的新化合物没有办法被制成相应制剂并在临床应用。学者们对药物的缓释制剂制备进行探索研究，做出了卓有成效的工作[7