Plackett-Burman设计结合响应面法优化可溶性微针的制备工艺  

Optimization of Preparation Process of Dissolving Microneedles by Plackett⁃Burman Design and Response Surface Analysis

作　　者：刘哲 刘勇 高广志 李奇贵 包阳阳 马凤森[1] LIU Zhe;LIU Yong;GAO Guangzhi;LI Qigui;BAO Yangyang;MA Fengsen(Laboratory of Biologicals and Biomaterials,College of Pharmacy,Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]浙江工业大学药学院生物制剂与材料实验室,杭州310014

出　　处：《材料导报》2021年第S02期593-599,共7页Materials Reports

基　　金：浙江省重点科技创新团队计划资助(2013TD15)。

摘　　要：研究了制备工艺对可溶性微针的机械、穿刺和吸湿性能的影响,并优化微针的制备工艺。采用Plackett-Burman设计筛选主要影响因素,运用Box-Behnken设计-响应面法优化微针的制备工艺。通过3D显微镜和扫描电子显微镜观察微针的外观形态,石蜡膜穿刺法评估微针的穿刺性能,称重法考察微针的吸湿性能,物性分析仪表征微针的机械性能,组织学切片验证微针穿刺皮肤的可行性。结果表明,微针韧脆材料比(P=0.0023)、药物占比(P=0.0075)、固化温度(P=0.0013)、空气流速(P=0.0027)和离心时间(P=0.0028)对穿刺性能具有显著影响;微针韧脆材料比(P=0.0177)对机械性能具有显著影响;各种因素对吸湿性能无显著影响。最优微针制备工艺参数为:韧脆材料比:9,50,药物占比:6.0%,溶媒占比60%,离心转速4000 r/min,离心时间28 min,离心温度25℃,干燥温度38℃,干燥湿度10%,空气流速0.5 L·min^(-1),微针的刺入深度为(412.03±2.85)μm,与预测值的偏差小于1%。最优微针的应力可达1.3 N/针,可成功刺破角质层。The aim of this study was to explore the influence of preparation process on the mechanical,puncture and moisture absorption performance of dissolving microneedles,and optimize the preparation process.The Plackett⁃Burman design was adopted to screen the major influential factors,then the preparation process of microneedles was optimized by Box⁃Behnken design⁃response surface methodology.3D microscope and scanning electron microscope were used to observe the morphological appearance of the microneedles.The puncture performance was examined by parafilm puncturing method,the moisture absorption performance was calculated by weighing method,and a texture analyzer was applied to investigate the mechanical properties,the feasibility of microneedles puncturing into the skin was verified by histological sections.The results showed that the ratio of tough and brittle material of the microneedles(P=0.0023),the percentage of the drug(P=0.0075),dry temperature(P=0.0013),air velocity(P=0.0027)and centrifugal time(P=0.0028)had a significant effect on the puncture performance,the ratio of tough and brittle material(P=0.0177)had a significant effect on the mechanical properties,and various parameters in the test had no significant in⁃fluence on the moisture absorption performance.The optimal preparation process parameters of microneedles was as follows,the ratio of the tough and brittle material was 9,50,the percentage of drug was 6.0%,the percentage of solvent was 60%,centrifugal speed was 4000 r/min,centrifugal time was 28 min,centrifugal temperature was 25℃,drying temperature was 38℃,drying humidity was 10%,air velocity was 0.5 L·min^(-1),the puncture depth of the microneedles was(412.03±2.85)μm,the deviation between the verification values and the predicted value was less than 1%.The force of the optimal microneedles can reach 1.3 N/needle,which can successfully puncture the stratum corneum.

关 键 词：PLACKETT-BURMAN设计 Box-Behnken设计-响应面法 可溶性微针 制备工艺 

分 类 号：R944.9[医药卫生—药剂学]