三维打印氯氮平口腔崩解片的片形优化与评价
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摘要
目的:采用三维打印技术在片形设计上对氯氮平口腔崩解片进行优化与评价。方法:根据打印层数-含药量回归方程计算目标剂量下对应的片剂体积。固定片剂体积,以片剂半径、外丝径宽、内丝径宽、打印层高为考察因素,以硬度和崩解时间为考察指标,采用综合评分法,对氯氮平口腔崩解片在片形上进行优化;将已优化的三维打印氯氮平口腔崩解片与国内市售氯氮平口腔崩解片在内部结构及体外溶出度方面进行评价。结果:最优片形设计下的氯氮平口腔崩解片在16. 0 s内崩解,含量均匀度符合规定,药物在1 min时累积溶出度达到96%。结论:已优化的三维打印氯氮平口腔崩解片崩解迅速,体外释放良好。
Objective: To optimize and evaluate the structural design of clozapine orally disintegrating tablets (ODT) by three-dimensional printing (3 DP) technique. Methods: The volume of tablet corresponding to the target dose was calculated according to the regression equation between the printing layer number and drug content. The formulation of clozapine ODT was optimized by employing orthogonal design with tablet radius,inner wire width,outer wire width and layer height as investigation factors,and hardness and disintegration time as evaluation indexes. Different structural models of the tablets were designed and optimized with the fixed volume.The inner structure,disintegration mechanism and in vitro dissolution of 3 DP clozapine ODTs were compared with those of commercial clozapine ODTs. Results: The clozapine ODTs with the optimized structure disintegrated in 16. 0 s,and the content uniformity met the requirements. The in vitro dissolution reached 96% within one minute.Conclusion: The optimized 3 DP clozapine ODT disintegrate rapidly and release well in vitro.
Objective: To optimize and evaluate the structural design of clozapine orally disintegrating tablets (ODT) by three-dimensional printing (3 DP) technique. Methods: The volume of tablet corresponding to the target dose was calculated according to the regression equation between the printing layer number and drug content. The formulation of clozapine ODT was optimized by employing orthogonal design with tablet radius,inner wire width,outer wire width and layer height as investigation factors,and hardness and disintegration time as evaluation indexes. Different structural models of the tablets were designed and optimized with the fixed volume.The inner structure,disintegration mechanism and in vitro dissolution of 3 DP clozapine ODTs were compared with those of commercial clozapine ODTs. Results: The clozapine ODTs with the optimized structure disintegrated in 16. 0 s,and the content uniformity met the requirements. The in vitro dissolution reached 96% within one minute.Conclusion: The optimized 3 DP clozapine ODT disintegrate rapidly and release well in vitro.
引文
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[2]URSAN ID,CHIU L,PIERCE A.Three-dimensional drug printing:a structured review[J].J Am Pharm Assoc,2013,53(2):136-144.
[3]LEE KJ,KANG A,DELFINO JJ,et al.Evaluation of critical formulation factors in the development of a rapidly dispersing captopril oral dosage form[J].Drug Dev Ind Pharm,2003,29(9):967-979.
[4]YU DG,SHEN XX,BRANFORD-WC,et al.Novel oral fast-disintegrating drug delivery devices with predefined inner structure fabricated by three-dimensional printing[J].J Pharm Pharmacol,2009,61(3):323-329.
[5]林启凤,杨帆,范凯燕,等.3D打印速效救心口崩片的制备研究[J].广东药学院学报,2016,32(1):1-4.
[6]田盼,黄思玉,杨帆,等.星点设计-效应面法优化三维打印片处方[J].中国新药杂志,2018,27(10):1188-1193.
[7]曾德志,樊学文,王兵华.氯氮平口崩片治疗难治性精神分裂症临床观察[J].湖北科技学院学报·医学版,2012,26(6):494-496.
[8]蒋丽红.氯氮平口腔崩解片与氯氮平普通片治疗精神分裂症的对照研究[J].中国医药指南,2013,11(25):478-479.
[9]赵淑芝,李聪慧.氯氮平口腔崩解片与氯氮平片治疗难治性精神分裂症观察分析[J].中国民康医学,2014,26(12):66-67.
[10]国家药典委员会.中华人民共和国药典[M].2015年版.第四部.北京:中国医药科技出版社,2015:124-125.
[11]国家药典委员会.中华人民共和国药典[M].2015年版.第四部.北京:中国医药科技出版社,2015:119.
[12]SKOWYRA J,PIETRZAK K,ALHNAN MA.Fabrication of extended-release patient-tailored prednisolone tablets via fused depositionmodelling(FDM)3D printing[J].Eur J Pharm Sci,2015,68:11-17.
[13]王欢欢,徐风华.综合评分法优选银花清咽片处方[J].中国药房,2012,23(19):1762-1764.
[14]王玮,廖维,朱少璇,等.综合评分法在阿德福韦酯分散片处方筛选中的应用[J].中国医院药学杂志,2011,31(12):1001-1003.
[15]国家药典委员会.中华人民共和国药典[S].2015年版.二部.北京:中国医药科技出版社,2015:1390.
[16]张彧,曾环想,袁鹰.复方格列本脲片的试制[J].中国新药杂志,2002,11(6):464-466.
[17]连王权,申宝德,沈成英,等.美洛昔康口腔速溶膜的制备及体外释放特性[J].中国新药杂志,2017,26(20):2478-2484.