黄体酮透皮贴剂和微针组合制剂的处方工艺和体外性质研究  

Prescription process and in vitro study of transdermal patch and microneedle combination formulation of progesterone

作　　者：刘灿 贺宏吉 苏文君 黄佳敏 董雪 沈琪[1,3,4] 王梅[1,3,4] LIU Can;HE Hong-ji;SU Wen-jun;HUANG Jia-min;DONG Xue;SHEN Qi;WANG Mei(College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;Karamay Food and Drug Inspection Institute,Kelamayi 834000,China;Engineering Research Center of Xinjiang and Central Asian Medicine Resources,Ministry of Education,Urumqi 830017,China;Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology,Urumqi 830017,China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830017 [2]新疆克拉玛依市食品药品检验所,新疆克拉玛依834000 [3]新疆及中亚特色医药资源教育部工程研究中心,新疆乌鲁木齐830017 [4]新疆天然药物活性组分与释药技术重点实验室,新疆乌鲁木齐830017

出　　处：《药学学报》2025年第3期809-816,共8页Acta Pharmaceutica Sinica

基　　金：新疆维吾尔自治区自然科学基金项目(2021D01C287);新疆维吾尔自治区重大科技专项项目(2022A03007-4)。

摘　　要：本文旨在制备黄体酮压敏胶贴剂与微针组合制剂,优化处方,并考察其药物释放量。采用HPLC检测制剂中黄体酮含量,通过单因素实验和正交实验,以感官评价、黏附性、累积释放量、累积渗透量等为评价指标,优选出贴剂最佳处方,并用3D打印方法制备3种不同针高的微针,将贴剂与微针组合测定其累积渗透量,并与单纯贴剂进行对比。正交实验结果表明,贴剂最优处方为Duro-Tak 87-2677压敏胶(87.5%)、柠檬酸三丁酯(2%)、肉豆蔻酸异丙酯(5%)、二丁基羟基甲苯(0.5%),黄体酮含量(5%)。工艺验证结果表明,按照优化处方制备的贴剂成形性、黏附性良好。在经皮渗透试验中,24 h时空白组的累积渗透量为52.35±7.88μg·cm^(-2),处方贴剂的累积渗透量为200.17±6.15μg·cm^(-2),与500、750、1000μm微针组合贴剂的累积渗透量分别为226.01±7.46、278.78±6.59、422.95±16.81μg·cm^(-2)。动物实验经新疆医科大学实验动物伦理委员会批准(伦理批号:IACUC-20220725-8)。通过单因素实验和正交实验,筛选出最优贴剂处方,且贴剂与微针组合制剂的透皮渗透效果比单用更好,能有效增加了药物体外经皮渗透。以上研究为黄体酮透皮贴剂的应用提供了理论依据。To prepare a progesterone pressure-sensitive gel patch combined with a microneedle to enhance drug release,HPLC was used to determine the preparation's progesterone content.One-way and orthogonal experiments were used to optimize the patch's prescription.Adhesion,sensory evaluation,cumulative release,and cumulative penetration were used as evaluation indices.Three microneedles with varying needle heights were made using 3D printing,and the cumulative penetration of the patch and microneedles was calculated and compared with the patch alone.The orthogonal experiments showed that the optimal prescription for the patches was Duro-Tak 87-2677pressure-sensitive adhesive(87.5%),tributyl citrate(2%),isopropyl myristate(5%),dibutylated hydroxytoluene(0.5%),and drug(5%).The patches were prepared according to the optimized prescription,resulting in good patch formability and adhesion.In the transdermal penetration test,the cumulative penetration of the patch was 52.35±7.88μg·cm^(-2)at 24 h,and the cumulative penetration of the patch in combination with 500,750,and 1000μm microneedles was 226.01±7.46,278.78±6.59,422.95±16.81μg·cm^(-2),respectively.The experiment was approved by the Experimental Animal Ethics Committee of Xinjiang Medical University(IACUC-20220725-8).The optimal patch prescription was screened through one-way and orthogonal experiments,and the transdermal penetration effect of patch and microneedle combination preparation was better than that of single use,which can effectively increase the in vitro transdermal penetration of the drug,and the above study provides a theoretical basis for the application of transdermal patches of progesterone.

关 键 词：黄体酮 贴剂 微针 体外渗透 促渗剂 

分 类 号：R943[医药卫生—药剂学]