熔融沉积成型3D打印卡托普利与氢氯噻嗪复方片剂的制备与体外评价

doi:10.19723/j.issn.1671-167X.2022.03.026

摘要/Abstract

摘要：

目的: 探究以熔融沉积成型(fused deposition modeling, FDM)3D打印技术制备治疗高血压复方片剂的可行性, 并对所制备的FDM 3D打印复方片剂进行相关的体外质量评价。方法: 以聚乙烯醇(polyvinyl alcohol, PVA)丝材作为辅料, 设计了具有两个独立隔室的椭圆形片剂(长轴20 mm, 短轴10 mm, 高5 mm), 其层高为0.2 mm, 外壳厚为1.2 mm, 顶和底厚均为0.6 mm, 两个隔室间的隔断厚为0.6 mm。使用FDM 3D打印机进行打印; 以卡托普利(captopril, CTP)和氢氯噻嗪(hydrochlorothiazide, HCT)为模型药物, 将其分别填充在片剂的两个隔室内。以扫描电镜观察制剂的外观形态, 考察制剂的质量差异和硬度, 以高效液相色谱法测定制剂中的药物含量, 并用溶出仪对制剂的体外释药行为进行表征。结果: 所制备的FDM 3D打印复方片剂均形态良好, 无打印缺陷; 平均质量为(644.3±6.55) mg, 其中CTP含量为(52.3±0.26) mg, HCT含量为(49.6±0.74) mg。观察到CTP和HCT在体外的延迟释放, 延迟释药时间分别为20 min和40 min, 释药70%的时间分别在30 min和60 min内。结论: 采用FDM 3D打印技术成功制备了CTP和HCT复方片剂, 并且所打印的复方片剂质量良好。

关键词: 熔融沉积成型, 打印, 三维, 高血压, 复方合剂, 片剂

Abstract:

Objective: To explore the feasibility of preparing compound tablets for the treatment of hypertension by fused deposition modeling (FDM) 3D printing technology and to evaluate the quality of the printed compound tablets in vitro. Methods: Polyvinyl alcohol (PVA) filaments were used as the exci-pient to prepare the shell of tablet. The ellipse-shaped tablets (the length of major axes of ellipse was 20 mm, the length of the minor axes of ellipse was 10 mm, the height of tablet was 5 mm) with two separate compartments were designed and printed using FDM 3D printer. The height of layer was 0.2 mm, and the thickness of roof or floor was 0.6 mm. The thickness of shell was 1.2 mm, and the thickness of the partition wall between the two compartments was 0.6 mm. Two cardiovascular drugs, captopril (CTP) and hydrochlorothiazide (HCT), were selected as model drugs for the printed compound tablet and filled in the two compartments of the tablet, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by electronic scale. The hardness of the tablets was measured by a single-column mechanical test system. The contents of the drugs in the tablets were determined by high performance liquid chromatography (HPLC), and the dissolution apparatus was used to measure the in vitro drug release of the tablets. Results: The prepared FDM 3D printed compound tablets were all in good shape without printing defects. The average weight of the tablets was (644.3±6.55) mg. The content of CTP and HCT was separately (52.3±0.26) mg and (49.6±0.74) mg. A delayed in vitro release profile was observed for CTP and HCT, and the delayed release time for CTP and HCT in vitro was 20 min and 40 min, respectively. The time for 70% of CTP and HCT released was separately 30 min and 60 min. Conclusion: CTP and HCT compound tablets were successfully prepared by FDM 3D printing technology, and the printed tablets were of good qualities.

Key words: Fused deposition modeling, Printing, three-dimensional, Hypertension, Drug combinations, Tablets

中图分类号:

R944.4

李志胜,钱浩楠,范田园. 熔融沉积成型3D打印卡托普利与氢氯噻嗪复方片剂的制备与体外评价[J]. 北京大学学报（医学版）, 2022, 54(3): 572-577.

Zhi-sheng LI,Hao-nan QIAN,Tian-yuan FAN. Preparation and in vitro evaluation of fused deposition modeling 3D printed compound tablets of captopril and hydrochlorothiazide[J]. Journal of Peking University (Health Sciences), 2022, 54(3): 572-577.

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参考文献 21

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Number	1	2	3	4	5	6	7	8	9	10
Weight/mg	652.5	632.7	645.6	652.7	650.6	633.9	642.6	644.2	642.9	646.0
Weight variation/%	1.27	-1.80	0.20	1.30	0.98	-1.61	-0.26	-0.02	-0.22	0.22