基于直接压片的多孔核壳粒子优化和应用

doi:10.5246/jcps.2024.05.031

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (5): 412-429.DOI: 10.5246/jcps.2024.05.031

基于直接压片的多孔核壳粒子优化和应用

李哲¹^,^#, 肖燕琳¹^,^#, 朱琳², 刘文君³, 杨凌宇³, 金正吉¹, Abid Naeem¹, 朱卫丰¹, 冯怡¹^,⁴, 明良山¹^,^*()

^1. 江西中医药大学高等研究院现代中药制备教育部重点实验室, 江西南昌 330004
^2. 澳门大学中医药研究所, 澳门中医药研究发展中心, 中药品质研究国家重点实验室, 澳门
^3. 江中药业股份有限公司, 江西南昌 330049
^4. 上海中医药大学中药现代制备技术教育部工程研究中心, 上海 201203

收稿日期:2023-11-05 修回日期:2023-12-10 接受日期:2024-01-12 出版日期:2024-05-31 发布日期:2024-05-31
通讯作者: 明良山

Optimization and application of porous core-shell particles for direct compaction

Zhe Li¹^,^#, Yanlin Xiao¹^,^#, Lin Zhu², Wenjun Liu³, Lingyu Yang³, Zhengji Jin¹, Abid Naeem¹, Weifeng Zhu¹, Yi Feng¹^,⁴, Liangshan Ming¹^,^*()

¹ Key Laboratory of Modern Preparation of TCM, Ministry of Education, Institute for Advanced Study, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi, China
² Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
³ Jiangzhong Pharmaceutical Co. Ltd., Nanchang 330049, Jiangxi, China
⁴ Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received:2023-11-05 Revised:2023-12-10 Accepted:2024-01-12 Online:2024-05-31 Published:2024-05-31
Contact: Liangshan Ming
About author:
^# Zhe Li and Yanlin Xiao contributed equally to this work.
Supported by:
National Natural Science Foundation of China (Grant No. 82003953, 82360777), China Postdoctoral Science Foundation (Grant No. 2019M662278), National Natural Science Foundation of Jiangxi Province (Grant No. 20202BAB216039, 20232ACB216015, 20212BAB216009 and 20232BAB206166), 2020-2022 Young Talents Support Project of Chinese Society of Chinese Medicine (Grant No. 2020-QNRC2-07), Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program (Grant No. CXTD-22004), and Doctoral Research start-up Fund Project of Jiangxi University of Chinese Medicine (Grant No. 2021BSZR015, 2022BSZR003).

摘要/Abstract

摘要：

采用中心复合设计优化了影响多孔型核壳复合颗粒(PCPs)直接压片(DC)性能的配方参数。分别以PVP和NH₄HCO₃作为壳层材料和制孔剂, 选择共喷雾干燥为制备工艺。以PCPs的产率、流动性、压缩性和崩解时间作为响应值。结果表明, NH₄HCO₃和PVP K30的最佳配比分别为4.76%和9.42%。产率、流动性、压缩性和崩解时间的测定值分别为62.00%、38.50°、4.02 MPa和14.33 min。预测误差分别为2.99%、1.09%、5.70%和2.28%。在本研究中, 最优的PCPs与四种DC辅料混合用于连续DC。结果表明, 优化后的PCPs具有优良的直压性能和适用性, 为其他中药制备PCPs及实现DC提供思路和理论支持。

关键词: 多孔型核壳复合粒子, 优化, 喷雾干燥, 直接压片, 应用

Abstract:

Xiao Er Xi Shi formulation powder (XEXS) is often used to treat indigestion for children and its extract powders have poor functional properties. In order to prepare XEXS-PCPs (porous core-shell composite particles) with optimal properties, the central composite design was used to optimize the formulation parameters that affect the direct compaction (DC) properties of PCPs based on XEXS. The proportions of shell material and pore-forming agent were taken as independent variables, and the yield, flowability, compactibility and disintegration time of PCPs were used as the response values. It was found that the best proportions of NH₄HCO₃ and PVP K30 were 4.76% and 9.42%, respectively. Furthermore, the measured values of yield, flowability, compactibility and disintegration time were 62.00%, 38.50°, 4.02 MPa and 14.33 min, respectively. The prediction errors were 2.99%, 1.09%, 5.70 % and 2.28%, respectively. In the present study, the optimal PCPs were mixed with four DC-grade excipients for continuous DC. The results showed that the optimal PCPs had excellent DC properties and applicability. It provides ideas and theoretical support for preparing PCPs and realizing DC for other traditional Chinese medicine.

Key words: Porous core-shell composite particles, Optimization, Spray drying, Direct compaction, Application

Supporting:

李哲, 肖燕琳, 朱琳, 刘文君, 杨凌宇, 金正吉, Abid Naeem, 朱卫丰, 冯怡, 明良山. 基于直接压片的多孔核壳粒子优化和应用[J]. 中国药学(英文版), 2024, 33(5): 412-429.

Zhe Li, Yanlin Xiao, Lin Zhu, Wenjun Liu, Lingyu Yang, Zhengji Jin, Abid Naeem, Weifeng Zhu, Yi Feng, Liangshan Ming. Optimization and application of porous core-shell particles for direct compaction[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(5): 412-429.

图/表 19

Table 1. 23 Central composite design of experiment.

Table 2. The central composite design plan and results.

Figure 1. The scanning electron photomicrographs of XEXS. (a) XEXS; (b) Ps-X-NH4; (c) PCPs-X-P-NH4.

Figure 2. Summary of Y1–Y4 fitting curves. (a) Fitting curve of yield of the composite particles; (b) Fitting curve of AR of the composite particles; (c) Fitting curve of TS of the composite particles; (d) Fitting curve of DT of the composite particles.

Table 3. Statistical summary of Y1.

Figure 3. Interaction effects affecting the yield of PCPs.

Table 4. Statistical summary of Y2.

Table 5. Powder flowability evaluation and corresponding AR.

Figure 4. Interaction effects affecting the flowability of PCPs.

Table 6. Statistical summary of Y3.

Figure 5. Interaction effects affecting the compactibility of PCPs.

Table 7. Statistical summary of Y4.

Figure 6. Interaction effects affecting the disintegration time of PCPs.

Figure 7. XEXS optimization scenario prediction profiler.

Table 8. Validation results of optimized response values.

Figure 8. Tensile strength profiles of four DC excipients (Mean ± SD, n = 3).

Figure 9. (a) The tensile strength profiles for XEXS and Cellactose with different drug loading (Mean ± SD, n = 3); (b) The tensile strength profiles for XEXS and MCC with different drug loading (Mean ± SD, n = 3).

Figure 10. The tensile strength profiles for XEXS with different drug loading (Mean ± SD, n = 3). (a), 3 KN; (b), 6 KN; (c), 9 KN; (d), 12 KN; TS, tensile strength; XEXS, PCPs-X-P-NH4; CL80, Cellactose 80; MCC; microcrystalline cellulose.

Table 9. The application of the mixture of the optimal PCPs-X-P-NH4 and DC-grade excipient for continuous DC.

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基于直接压片的多孔核壳粒子优化和应用

Optimization and application of porous core-shell particles for direct compaction

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