利用半固体挤压3D打印技术制备两种穿心莲内酯缓释制剂

doi:10.5246/jcps.2023.11.075

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (11): 935-946.DOI: 10.5246/jcps.2023.11.075

利用半固体挤压3D打印技术制备两种穿心莲内酯缓释制剂

李永圆¹^,^#, 谢茂梅¹^,^#, 陈晨¹, 文有青¹, 颜月玲¹, 王海霞¹^,²^,^*()

1. 天津中医药大学中药制药工程学院, 天津 301617
2. 天津中医药大学组分中药国家重点实验室, 天津 301617

收稿日期:2023-03-23 修回日期:2023-04-24 接受日期:2023-06-04 出版日期:2023-12-02 发布日期:2023-12-02
通讯作者: 王海霞
作者简介:
+ Tel.: +86-022-59791811, E-mail: whxtcm@tjutcm.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 82003944) and the Science and Technology Plan Project of Tianjin (Grant No. 22YDTPJC00380).

Preparation of two sustained-release formulations of andrographolide by semi-solid extrusion 3D printer

Yongyuan Li¹^,^#, Maomei Xie¹^,^#, Chen Chen¹, Youqing Wen¹, Yueling Yan¹, Haixia Wang¹^,²^,^*()

1 College of Pharmaceutical Engineering of Traditional Chinese Medicine (TCM), Tianjin University of TCM, Tianjin 301617, China
2 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of TCM, Tianjin 301617, China

Received:2023-03-23 Revised:2023-04-24 Accepted:2023-06-04 Online:2023-12-02 Published:2023-12-02
Contact: Haixia Wang
About author:
# Yongyuan Li and Maomei Xie contributed equally to this work.

摘要/Abstract

摘要：

为了满足不同人群的用药需求, 采用半固态挤出(SSE)型3D打印技术制备了不同释放速率的穿心莲内酯片(3D-AGT)和包封剂(3D-AGE)两种制剂。首先利用海藻酸钠和壳聚糖作为载药基质, 成功打印出直径为10.00 mm, 高度为3.00 mm的六棱柱状3D-AGT片剂。然后通过上壳和载药底座的无缝组装获得了3D-AGE包封剂。两种制剂表面光滑, 质地均匀。FT-IR结果显示, 打印过程并没有破坏穿心莲内酯和辅料的化学结构。由四种不同辅料配比的3D-AGT片剂的药物装载量均在85%以上。同时, 载药量为10和20 mg的两种药物装载量的3D-AGE制剂也被成功制备。体外溶出度结果表明, 相比于市售制剂, 3D-AGT和3D-AGE两种制剂均显示出了一定的药物缓慢释放性能, 但药物释放活性受辅料配比和载药量的影响不明显。体外抑菌实验表明两种制剂对大肠杆菌体外抑菌率均在85%以上。此外, 9名志愿者的适口性实验结果表明3D-AGE制剂对穿心莲的苦味具有一定的掩盖作用。本研究表明通过有效的结构设计和调整打印参数, 可以基于3D打印技术对穿心莲内酯制剂的释放速率进行调控, 这也为个性化中药制剂的制备提供了一种新方法。

关键词: 半固体挤压, 3D打印, 穿心莲内酯, 释放速率, 掩味性

Abstract:

To address the medication requirements of different populations, efforts have been made to develop sustained-release formulations of andrographolide. In this study, andrographolide tablets (3D-AGT) and encapsulating agents (3D-AGE) were created using a semi-solid extrusion (SSE) 3D printer with varying release rates. Sodium alginate and chitosan were utilized as excipients to produce a hexagonal 3D-AGT with a diameter of 10.00 mm and a height of 3.00 mm. The 3D-AGE was then assembled by combining the upper layer and the ground floor loaded with andrographolide. Both formulations exhibited smooth surfaces and uniform internal composition. FT-IR analysis confirmed that the chemical structures of andrographolide and the excipients remained intact throughout the printing process. The drug loading capacity of 3D-AGT preparations, formulated with four different excipient ratios, exceeded 85%. Additionally, two 3D-AGE preparations (10 and 20 mg) were successfully loaded with the drug. In vitro drug release tests demonstrated that both 3D-AGT and 3D-AGE preparations exhibited satisfactory drug release performance. However, the proportions of excipients and drug loading had minimal impact on the cumulative drug dissolution effect. In terms of antibacterial activity against Escherichia coli, both preparations displayed antibacterial rates of nearly 85% or higher in vitro. Furthermore, the average results from nine volunteers indicated that 3D-AGE effectively masked the bitter taste of andrographolide. This study suggested that the release rate of andrographolide could be regulated using SSE 3D printing through careful structural design and adjustment of printing parameters, thus providing a novel approach for personalized traditional Chinese medicine preparations.

Key words: Semi-solid extrusion, 3D printing, Andrographolide, Release rate, Taste masking

Supporting: /Jwk3_zgyxen/attached/file/20231206/20231206224827_350.pdf

李永圆, 谢茂梅, 陈晨, 文有青, 颜月玲, 王海霞. 利用半固体挤压3D打印技术制备两种穿心莲内酯缓释制剂[J]. 中国药学(英文版), 2023, 32(11): 935-946.

Yongyuan Li, Maomei Xie, Chen Chen, Youqing Wen, Yueling Yan, Haixia Wang. Preparation of two sustained-release formulations of andrographolide by semi-solid extrusion 3D printer[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(11): 935-946.

图/表 11

Table 1. The material ratio of excipients and printing effect of 3D-AGT.

Table 2. The material ratio of excipients and printing effect of 3D-AGE.

Table 3. Dimensions of the upper shell and the ground floor of 3D-AGE.

Figure 1. The upper shell (A) and the ground floor (B) models of 3D-AGE.

Figure 2. The appearance of 3D-AGT (A, B, C) and 3D-AGE (D, E, F) from different angles (F: 3D-AGE loaded with andrographolide).

Figure 3. Left: SEM images of the surface (A), side (B), cross-section (C) and longitudinal section (D) of the 3D-AGT; Right: SEM images of the surface (A), sides (B), sections (C) and corners (D) of the 3D-AGE.

Figure 4. XRD patterns of 3D-AGT and 3D-AGE (A); FT-IR of three kinds of excipients, 3D-AGT and 3D-AGE (B); drug content histogram of 3D-AGE (C).

Table 4. Infrared characteristic peaks of 3D-AGT and 3D-AGE.

Table 5. The drug loading rate of 3D-AGT with different excipient ratios.

Figure 5. Accumulative dissolution rate curves of 3D-AGT and commercially available tablets (RH, JR, ZT) in four media: phosphate solution (pH = 6.8, A), acetate solution (pH = 4.0, B), hydrochloric acid solution (pH = 1.2, C), and pure water (D).

Figure 6. Accumulative dissolution rate curves of 3D-AGE with different drug loading and commercially available capsule in water (A); bacteriostatic rate of 3D-AGT and 3D-AGE on E. coli (B); taste masking effect of 3D-AGE containing different drug loading (C).

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利用半固体挤压3D打印技术制备两种穿心莲内酯缓释制剂

Preparation of two sustained-release formulations of andrographolide by semi-solid extrusion 3D printer

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