[关键词]
[摘要]
目的 通过羟丙基-β-环糊精(HP-β-CD)包合樟脑(camphor,CA),解决CA在巴布剂工业化生产过程中易挥发损失的问题。方法 采用恒温搅拌法制备CA的HP-β-CD包合物(CA-HP-β-CD),以CA包合率为指标优化了CA-HP-β-CD制备工艺,并采用差示扫描量热仪(DSC)、紫外分光光度法(UV)和扫描电镜(SEM)对CA-HP-β-CD进行药剂学性质的考察表征;然后,以CA与CA-HP-β-CD的形式投料,在巴布剂工业化生产线上制备成巴布剂样品,再测定其中CA的含量,并进行统计分析。结果 当CA与HP-β-CD的物料比为1∶3,35℃条件下,以300 r/min搅拌4.0 h,采用恒温搅拌法制备的CA-HP-β-CD对CA的包合率为(68.57±1.26)%;DSC、UV与SEM扫描检测表明CA与HP-β-CD的相容性良好,CA能够被HP-β-CD充分包合并形成稳定的包合物CA-HP-β-CD。以CA-HP-β-CD投料,经工业化生产线制备后,CA在巴布剂中的留存率(实际含量/投料量)为(80.13±1.05)%;而以CA投料,则留存率为(39.45±1.38)%,二者之间存在显著性差异(t检验,P<0.01)。结论 将CA制备成HP-β-CD包合物,能够显著降低CA在巴布剂工业化制备过程的挥发损失,进而提高了CA的利用效率并降低了成本,为含有易挥发药物的巴布剂研发提供了思路借鉴。
[Key word]
[Abstract]
Objective To reduce or avoid the volatilization loss of camphor (CA) in the industrialized preparation of cataplasm, using the inclusion technology of HP-β-CD. Methods The HP-β-CD inclusion compound of CA (CA-HP-β-CD) was prepared by the constant temperature stirring method. The preparation processing of CA-HP-β-CD was optimized with inclusion efficiency as an index, and the pharmaceutical properties of CA-HP-β-CD were characterized by DSC, UV and SEM. The CA and CA-HP-β-CD were prepared to cataplasm at the industrial-scale production respectively, then the content of CA was determined and the statistical analysis was carried out. Results The inclusion efficiency of CA-HP-β-CD for CA was (68.57±1.26)% when the CA-HP-β-CD was prepared with the mass ratio of CA to HP-β-CD 1:3, the working temperature at 35℃ and stirring at 300 r/min for 4.0 h. The DSC, UV and SEM scans showed that there was a good compatibility between CA and HP-β-CD, and CA could be fully encapsulated by HP-β-CD and formed a stable inclusion complex of CA-HP-β-CD. Results of industrial-scale production of cataplasm for CA and CA-HP-β-CD revealed that the retention rate (actual content/feeding quantity) were (80.13±1.05)% and (39.45±1.38)%, respectively. And there was a statistically significant difference between them (t-test, P<0.01), indicating that the HP-β-CD inclusion complex effectively reduce the volatilization loss of camphor CA. Conclusion The volatilization loss of CA at the industrial-scale production of cataplasm was effectively reduced by the CA-HP-β-CD, which improves the utilization rate of CA and reduces the cost, and provides ideas and reference for the research and development of cataplasm of volatile drugs.
[中图分类号]
R283.6
[基金项目]
陕西高校青年创新团队建设项目(陕教[2019]90号);陕西省中医药管理局科研课题(2019-ZZ-ZY010);陕西省教育厅自然科学基金项目(17JS120);陕西省教育厅自然科学基金项目(19JK0759);西安医学院科研项目配套基金项目(2018PT58);西安医学院科研项目配套基金项目(2017GJFY10)