Design and Optimization of 3D Printing Amlodipine Besylate Chewable Tablets
HAN Xiao-lu1,2, HONG Xiao-xuan1, LIU Bo-shi1,3, ZHU Chun-xiao1, DU Yi-meng1, ZHANG Hui1, GAO Jing1, WANG Zeng-ming1*, ZHENG Ai-ping1*
1. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China; 2. Troops 32104 of People's Liberation Army of China, Alashan 735400, China; 3. Military Hospital 93152 of People's Liberation Army of China, Tonghua 135300, China
Abstract：OBJECTIVE To develop a semi-solid materialfor 3D printing technology based on the concept of quality by design(QbD). METHODS Amlodipine besylate was used as the model drug, CMC-NA, CMS-Na and glycerin were used as independent variables, and hardness, fragility, disintegration and dissolution were used as dependent variables. The full factor design of 23 was used to establish the design space of the prescription, and the amplification study was carried out. RESULTS The semi-solid material has good printability. In the design space, 1.0% CMC-NA, 7.0%CMS-Na and 10.0% glycerin were selected for amplification. All the indexes were close to the predicted values of the model and all met the requirements. CONCLUSION The total factorial experimental design can be used for the prescription optimization of 3D printed semi-solid materials, and the optimized prescription can meet the preparation requirements of 3D printed chewable tablets, which provides the possibility for the mass production of extruded 3D printing and the realization of personalized customized drugs.
A C G, V D C I,WAYNE W C. Amlodipine: A new calcium antagonist[J]. Am J Hosp Pharm, 1994, 51(1): 59-68.
LURBE E, CIFKOVA R, CRUICKSHANK J K, et al. Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension[J]. J Hypertension, 2009, 27(9): 1719-1742.
VAN D V A. C, VAN D V I, SMEETS O S N M, et al. Design and stability study of an oral solution of amlodipine besylate for pediatric patients[J]. Eur J Pharm, 2016, 92(92):220-223.
GHITZA U E. A Commentary on "a new initiative on precision medicine"[J]. Front Psychiatry, 2015, 6(5): 88-90.
ZHANG H X, YOU J. Aspirin bilayer tablets prepared with 3D printer for drug controlled release [J]. Chin Pharm J(中国药学杂志), 2017, 52(4): 298-302.
LIU B S, WANG Z M, ZHANG H, et al. Application of "Quality by Design"in the preparation of acetaminophen sustained-release tablets by 3D printing [J]. Acta Pharm Sin(药学学报), 2020, 55(11): 2719-2727.
ZENG Q Y, YANG M R, GU Y P, et al. Preparation and optimizing formulation of simvastatin tablets by 3D printing [J]. Chin Pharm J(中国药学杂志), 2020, 55(10): 843-848.
KLINGMANN V, SPOMER N, LERCH C, et al. Favorable acceptance of mini-tablets compared with syrup: a randomized controlled trial in infants and preschool children[J]. J Pediatr, 2013, 163(6):1728-1732.
COLLINS F S,VARMUS H. A new initiative on precision medicine[J]. N Engl J Med, 2015, 372(9): 793-798.
GODOI F C, PRAKASH S, BHANDARI B R. 3D printing technologies applied for food design: status and prospects[J]. J Food Eng, 2016,179(179): 44-54.
B C F G A, D M Z A,C B B. A comparative study between syringe-based and screw-based 3D food printers by computational simulation[J]. Comput Elec Agr, 2019, 162(162): 397-404.
CUI M, LI Y, WANG S, et al. Exploration and preparation of a dose-flexible regulation system for levetiracetam tablets via novel semi-solid extrusion three-dimensional printing[J]. J Pharm Sci, 2019, 108(2): 977-986.
LI D, WANG S J. Optimization of wax matrix sustained release tablets based on QBD [J]. J Shenyang Pharm Univ(沈阳药科大学学报), 2020, 37(2): 97-105.
WANG Y, MIAO Y, ZHANG J, et al. Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery[J]. Mater Sci Eng C Mater Biol Appl, 2018, 84(5): 44-51.
LI M T, LIU Q, ZHANG Y Q, et al. Preparation and characterization of ternary indomethacin solid dispersion based on quality by design (QbD) concept [J]. Chin Pharm J(中国药学杂志), 2020, 55(17): 1450-1455.
JIANG X W, FEI Y Y, LIAN G Y, et al. Design and optimization of the formulation and technology of theophylline gel matrix sustained-release tablets based on QbD concept [J]. J China Pharm(中国药房), 2019, 30(18):2502-2507.