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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (2): 348-354. doi: 10.19723/j.issn.1671-167X.2021.02.020

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Preparation and in vitro evaluation of fused deposition modeling 3D printed verapa-mil hydrochloride gastric floating formulations

CHEN Di1,XU Xiang-yu2,WANG Ming-rui1,LI Rui1,ZANG Gen-ao2,ZHANG Yue1,QIAN Hao-nan1,YAN Guang-rong2,Δ(),FAN Tian-yuan1,Δ()   

  1. 1. Department of Pharmaceutics, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
    2. School of Mechanical Engineering and Automation, Beihang University, Beijing 100191, China
  • Received:2019-05-05 Online:2021-04-18 Published:2021-04-21
  • Contact: Guang-rong YAN,Tian-yuan FAN E-mail:yangr@buaa.edu.cn;tianyuan_fan@bjmu.edu.cn

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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

CLC Number: 

  • R944.9

Figure 1

Schematic diagram of FDM 3D printed gastric floating formulations A, C, capsule; B, D, hemisphere. a and b represent the length and height of the formulations, respectively."

Figure 2

Illustration of the infill structure of the FDM 3D printed gastric floating formulations A, capsule; B, hemisphere."

Table 1

Parameters of the FDM 3D printed gastric floating formulations"

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

Figure 3

Illustration of the applied force in two perpendicular directions (direction Ⅰ and direction Ⅱ) measuring the hardness of the formulations"

Figure 4

Photos of the FDM 3D printed gastric floating formulations A, appearance of capsule; B, section of capsule; C, appearance of he-misphere; D, section of hemisphere."

Figure 5

SEM images of the FDM 3D printed gastric floating formulations A, surface of capsule; B, section of capsule; C, surface of hemisphere; D, section of hemisphere."

Table 2

Characterization results of the FDM 3D printed gastric floating formulations"

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

Figure 6

In vitro drug release curves of conventional tablet, capsule and hemisphere FDM 3D printed gastric floating formulations"

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