熔融沉积成型3D打印盐酸维拉帕米胃漂浮制剂的制备与体外评价

doi:10.19723/j.issn.1671-167X.2021.02.020

摘要/Abstract

摘要：

目的: 探究以熔融沉积成型(fused deposition modeling,FDM)3D打印技术研制胃漂浮制剂的可行性,并对所研制的FDM 3D打印胃漂浮制剂进行相关的体外质量评价。方法: 以盐酸维拉帕米为模型药物,聚乙烯醇(polyvinyl alcohol,PVA)为辅料,利用FDM 3D打印技术制备胶囊型和半球型的两种胃漂浮制剂,其填充率均为15%,层高均为0.2 mm,顶底厚均为0.8 mm,壳数分别为3和4。以扫描电镜观察制剂的形态,以称重法考察制剂的平均质量,采用物性测定仪测定制剂互相垂直的两个方向的硬度,高效液相色谱法测定制剂中的药物含量,并对制剂的体外漂浮和释药行为进行表征。结果: 所制备的FDM 3D打印胶囊型和半球型制剂均形态良好,无打印缺陷;胶囊型和半球型制剂的平均质量分别为(584±13) mg和(550±12) mg;胶囊型和半球型制剂的硬度均大于800.0 N;胶囊型和半球型制剂均实现了体外漂浮且无漂浮滞后时间,体外漂浮时间分别为(3.97±0.41) h和(4.48±0.21) h;胶囊型和半球型制剂在体外释药完全的时间均为3 h。结论: 采用FDM 3D打印技术成功制备了胶囊型和半球型的盐酸维拉帕米胃漂浮制剂。

关键词: 熔融沉积成型, 打印, 三维, 维拉帕米, 胃漂浮制剂

Abstract:

Objective: To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. Methods: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. Results: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. Conclusion: The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.

Key words: Fused deposition modeling, Printing, three-dimensional, Verapamil, Gastric floating formulation

中图分类号:

R944.9

陈迪,徐翔宇,汪明睿,李芮,臧根奥,张悦,钱浩楠,闫光荣,范田园. 熔融沉积成型3D打印盐酸维拉帕米胃漂浮制剂的制备与体外评价[J]. 北京大学学报（医学版）, 2021, 53(2): 348-354.

CHEN Di,XU Xiang-yu,WANG Ming-rui,LI Rui,ZANG Gen-ao,ZHANG Yue,QIAN Hao-nan,YAN Guang-rong,FAN Tian-yuan. Preparation and in vitro evaluation of fused deposition modeling 3D printed verapa-mil hydrochloride gastric floating formulations[J]. Journal of Peking University (Health Sciences), 2021, 53(2): 348-354.

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Formulations	Size/mm		Layer height/mm	Floor or roof thickness/mm	Number of shells	Infill percentage/%
Formulations	a	b	Layer height/mm	Floor or roof thickness/mm	Number of shells	Infill percentage/%
Capsule	17.7	6.8	0.2	0.8	3	15
Hemisphere	11.4	7.8	0.2	0.8	4	15

Formulations	Weight/mg	Hardness/N		Lag time/s	Floating time/h
Formulations	Weight/mg	Direction Ⅰ	Direction Ⅱ	Lag time/s	Floating time/h
Capsule	584±13	>800.0	>800.0	0	3.97±0.41
Hemisphere	550±12	>800.0	>800.0	0	4.48±0.21