3D Printing of a Multi-Layered Polypill Containing Six Drugs Using a Novel Stereolithographic Method

被引:243
作者
Robles-Martinez, Pamela [1 ]
Xu, Xiaoyan [1 ]
Trenfield, Sarah J. [1 ]
Awad, Atheer [1 ]
Goyanes, Alvaro [2 ,3 ]
Telford, Richard [4 ]
Basit, Abdul W. [1 ,2 ]
Gaisford, Simon [1 ,2 ]
机构
[1] UCL, UCL Sch Pharm, Dept Pharmaceut, 29-39 Brunswick Sq, London WC1N 1AX, England
[2] FabRx Ltd, 3 Romney Rd, Ashford TN24 0RW, Kent, England
[3] Univ Santiago de Compostela, Dept Farmacol Farm & Tecnol Farmaceut, RD Pharma Grp GI 1645, Santiago De Compostela 15782, Spain
[4] Univ Bradford, Sch Chem & Forens Sci, Richmond Rd, Bradford BD7 1DP, W Yorkshire, England
基金
英国工程与自然科学研究理事会;
关键词
three-dimensional printing; fixed-dose combinations; additive manufacturing; 3D printed drug products; printlets; tablets; personalized medicines; multiple-layer dosage forms; stereolithography; vat polymerisation; COMBINATION THERAPY; INNOVATIVE APPROACH; IMPROVE ADHERENCE; DOSAGE FORMS; RELEASE; TABLETS; FORMULATIONS; TECHNOLOGIES; PREDNISOLONE; FABRICATION;
D O I
10.3390/pharmaceutics11060274
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Three-dimensional printing (3DP) has demonstrated great potential for multi-material fabrication because of its capability for printing bespoke and spatially separated material conformations. Such a concept could revolutionise the pharmaceutical industry, enabling the production of personalised, multi-layered drug products on demand. Here, we developed a novel stereolithographic (SLA) 3D printing method that, for the first time, can be used to fabricate multi-layer constructs (polypills) with variable drug content and/or shape. Using this technique, six drugs, including paracetamol, caffeine, naproxen, chloramphenicol, prednisolone and aspirin, were printed with different geometries and material compositions. Drug distribution was visualised using Raman microscopy, which showed that whilst separate layers were successfully printed, several of the drugs diffused across the layers depending on their amorphous or crystalline phase. The printed constructs demonstrated excellent physical properties and the different material inclusions enabled distinct drug release profiles of the six actives within dissolution tests. For the first time, this paper demonstrates the feasibility of SLA printing as an innovative platform for multi-drug therapy production, facilitating a new era of personalised polypills.
引用
收藏
页数:16
相关论文
共 65 条
[1]   Emergence of 3D Printed Dosage Forms: Opportunities and Challenges [J].
Alhnan, Mohamed A. ;
Okwuosa, Tochukwu C. ;
Sadia, Muzna ;
Wan, Ka-Wai ;
Ahmed, Waqar ;
Arafat, Basel .
PHARMACEUTICAL RESEARCH, 2016, 33 (08) :1817-1832
[2]   Printing T3 and T4 oral drug combinations as a novel strategy for hypothyroidism [J].
Alomari, Mustafa ;
Vuddanda, Parameswara R. ;
Trenfield, Sarah J. ;
Dodoo, Cornelius C. ;
Velaga, Sitaram ;
Basit, Abdul W. ;
Gaisford, Simon .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2018, 549 (1-2) :363-369
[3]   Personalised dosing: Printing a dose of one's own medicine [J].
Alomari, Mustafa ;
Mohamed, Fatima H. ;
Basit, Abdul W. ;
Gaisford, Simon .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2015, 494 (02) :568-577
[4]   3D Printed Pellets (Miniprintlets): A Novel, Multi-Drug, Controlled Release Platform Technology [J].
Awad, Atheer ;
Fina, Fabrizio ;
Trenfield, Sarah J. ;
Patel, Pavanesh ;
Goyanes, Alvaro ;
Gaisford, Simon ;
Basit, Abdul W. .
PHARMACEUTICS, 2019, 11 (04)
[5]   3D printed medicines: A new branch of digital healthcare [J].
Awad, Atheer ;
Trenfield, Sarah J. ;
Gaisford, Simon ;
Basit, Abdul W. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2018, 548 (01) :586-596
[6]   Reshaping drug development using 3D printing [J].
Awad, Atheer ;
Trenfield, Sarah J. ;
Goyanes, Alvaro ;
Gaisford, Simon ;
Basit, Abdul W. .
DRUG DISCOVERY TODAY, 2018, 23 (08) :1547-1555
[7]   Fixed-dose combinations improve medication compliance: A meta-analysis [J].
Bangalore, Sripal ;
Kamalakkannan, Gayathri ;
Parkar, Sanobar ;
Messerli, Franz H. .
AMERICAN JOURNAL OF MEDICINE, 2007, 120 (08) :713-719
[8]  
Basit A., 2018, 3D printing of pharmaceuticals
[9]   3D printed tablets loaded with polymeric nanocapsules: An innovative approach to produce customized drug delivery systems [J].
Beck, R. C. R. ;
Chaves, P. S. ;
Goyanes, A. ;
Vukosavljevic, B. ;
Buanz, A. ;
Windbergs, M. ;
Basit, A. W. ;
Gaisford, S. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2017, 528 (1-2) :268-279
[10]   A Polypill Strategy to Improve Adherence Results From the FOCUS Project [J].
Castellano, Jose M. ;
Sanz, Gines ;
Penalvo, Jose L. ;
Bansilal, Sameer ;
Fernandez-Ortiz, Antonio ;
Alvarez, Luz ;
Guzman, Luis ;
Carlos Linares, Juan ;
Garcia, Fernando ;
D'Aniello, Fabiana ;
Albert Arnaiz, Joan ;
Varea, Sara ;
Martinez, Felipe ;
Lorenzatti, Alberto ;
Imaz, Inaki ;
Sanchez-Gomez, Luis M. ;
Carla Roncaglioni, Maria ;
Baviera, Marta ;
Smith, Sidney C., Jr. ;
Taubert, Kathryn ;
Pocock, Stuart ;
Brotons, Carlos ;
Farkouh, Michael E. ;
Fuster, Valentin .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 64 (20) :2071-2082