盐酸胍法辛缓释给药系统的构建及体内外评价

doi:10.5246/jcps.2025.12.080

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (12): 1063-1080.DOI: 10.5246/jcps.2025.12.080

• 【研究论文】 • 下一篇

盐酸胍法辛缓释给药系统的构建及体内外评价

何泽¹, 冯颖淑², Caleb Kesse Firempong¹, 芦静茹¹, 刘宏飞¹^,^*(), 于小凤¹^,^*()

^1. 江苏大学药学院, 江苏镇江 212013
^2. 镇江市高等专科学校医药技术学院, 江苏镇江 212028

收稿日期:2025-09-21 修回日期:2025-10-11 接受日期:2025-10-25 出版日期:2025-12-31 发布日期:2025-12-31
通讯作者: 刘宏飞, 于小凤

Development and comprehensive evaluation of a guanfacine hydrochloride extended-release drug delivery system: in vitro and in vivo insights

Ze He¹, Yingshu Feng², Caleb Kesse Firempong¹, Jingru Lu¹, Hongfei Liu¹^,^*(), Xiaofeng Yu¹^,^*()

¹ College of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China
² School of Pharmaceutical & Chemical Technology, Zhenjiang College, Zhenjiang 212028, Jiangsu, China

Received:2025-09-21 Revised:2025-10-11 Accepted:2025-10-25 Online:2025-12-31 Published:2025-12-31
Contact: Hongfei Liu, Xiaofeng Yu
Supported by:
The Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant No. SJCX24-2440), the 2021 Zhenjiang sixth “169 project” scientific research project, and the 2023 Qinglan Project of Jiangsu Province, China.

摘要/Abstract

摘要：

本研究在制备粒径分布窄的药用辅料阳离子交换树脂的基础上研制盐酸胍法辛缓释混悬液。采用离心界膜乳化技术对传统的悬浮聚合法进行改进, 制备粒径分布窄的阳离子交换树脂, 与市售树脂(Amberlite^® IRP69)相比, 自制树脂表面光滑, Span值为0.74。以该树脂为载体, 采用静态法制备盐酸胍法辛药物树脂复合物。采用乳化溶剂挥发法制备具有缓释效果的盐酸胍法辛包衣微囊。体外释放结果显示, GFN-CM 在10 h内的释放曲线与零级释放模型拟合效果最佳, 12 h的累计释放量为81.88%。新西兰兔体内药动学实验显示, 与市售盐酸胍法辛缓释片相比, GFN缓释混悬液的MRT_0–24由7.619 h延长至8.336 h, 药时曲线更加平稳, 平均相对生物利用度(F_r)为111.36%。本研究成功合成了一种粒径分布较窄的阳离子交换树脂, 为缓释给药体系的发展提供了新的思路与策略。

关键词: 盐酸胍法辛, 阳离子交换树脂, 离心界膜乳化技术, 乳化溶剂挥发法

Abstract:

In the present study, an extended-release (ER) suspension of guanfacine hydrochloride (GFN) was successfully formulated using a self-synthesized cation-exchange resin characterized by a narrow particle size distribution. The drug-resin complex was prepared through a static adsorption method, employing the resin as a pharmaceutical carrier. Subsequently, guanfacine hydrochloride-coated microcapsules (GFN-CM) were fabricated via an emulsion solvent evaporation technique to achieve sustained-release functionality. Characterization revealed that the in-house resin exhibited a smoother surface and a narrower size distribution (Span value: 0.74) compared to the commercial counterpart, Amberlite^® IRP69. In vitro release studies demonstrated that the GFN-CM followed a zero-order kinetic model over 10 h, with a cumulative drug release of 81.88% observed at 12 h. Furthermore, pharmacokinetic evaluation in New Zealand rabbits showed that the mean residence time (MRT_0–24) of the GFN suspension extended from 7.619 to 8.336 h, displaying a more stable plasma concentration-time profile and an average relative bioavailability (F_r) of 111.36% compared to marketed ER GFN tablets. These findings highlighted the successful development of a novel cation exchange resin-based delivery system, offering a promising strategy for enhancing the performance of ER pharmaceutical formulations.

Key words: Guanfacine hydrochloride, Cation-exchange resin, Centrifugal boundary film emulsification, Emulsification-solvent evaporation method

Supporting:

何泽, 冯颖淑, Caleb Kesse Firempong, 芦静茹, 刘宏飞, 于小凤. 盐酸胍法辛缓释给药系统的构建及体内外评价[J]. 中国药学(英文版), 2025, 34(12): 1063-1080.

Ze He, Yingshu Feng, Caleb Kesse Firempong, Jingru Lu, Hongfei Liu, Xiaofeng Yu. Development and comprehensive evaluation of a guanfacine hydrochloride extended-release drug delivery system: in vitro and in vivo insights[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(12): 1063-1080.

图/表 19

Figure 1. Structure of GFN.

Table 1. GFN-CM prescriptions.

Figure 2. Infrared spectra of PS-DVB (a), Amberlite® IRP69 (b), and self-made resin (c).

Figure 3. Particle size distribution of Amberlite® IRP69 (a) and self-made resin (b).

Table 2. Particle size distribution data for Amberlite® IRP69 and self-made resin.

Figure 4. Appearance of Amberlite® IRP69 (a) and self-made resin (b).

Figure 5. Effect of GFN concentration on static method (a). Effect of temperature on static method (b). Effect of drug-resin ratio on static method (c). Ion exchange isotherm (d).

Figure 6. Ion exchange curves of Amberlite® IRP69 (a) and self-made resin (b).

Figure 7. Appearance and morphology of self-made resin (a), GFN (b), physical mixture (c), and GFN-DRC (d).

Figure 8. Infrared spectra of GFN (a), self-made resin (b), physical mixture (c), and GFN-DRC (d).

Figure 9. XRD patterns of self-made resin (a), GFN (b), physical mixture (c), and GFN-DRC (d).

Figure 10. SEM differences of GFN-DRC impregnation before and after coating.

Figure 11. Particle size distribution of GFN-CM.

Figure 12. Effect of different kinds of medium ions on drug release of GFN-DRC (a). Effect of ion intensity on the drug release of GFN-DRC (b). Effect of rotational speed on the drug release of GFN-DRC (c). Effect of medium volume on the drug release of GFN-DRC (d). Effect of medium temperature on the drug release of GFN-DRC (e).

Figure 13. In vitro release curves of commercially available GFN-DRC (a), self-made GFN-DRC (b), and GFN-CM (c) (75 r/min, 37 °C, n = 3).

Table 3. Fitting results of the GFN-CM release mechanism.

Figure 14. In vitro release curves for commercially available ER tablets and self-made ER suspensions (n = 3).

Figure 15. Drug time curve of self-made GFN suspension and commercially available GFN ER tablets in New Zealand rabbits.

Table 4. Pharmacokinetic parameters of GFN self-made suspension and commercially available GFN ER tablets.

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盐酸胍法辛缓释给药系统的构建及体内外评价

Development and comprehensive evaluation of a guanfacine hydrochloride extended-release drug delivery system: in vitro and in vivo insights

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