头孢妥仑生物黏附缓释干混悬剂的制备及体内外评价

doi:10.5246/jcps.2026.01.004

中国药学(英文版) ›› 2026, Vol. 35 ›› Issue (1): 54-70.DOI: 10.5246/jcps.2026.01.004

头孢妥仑生物黏附缓释干混悬剂的制备及体内外评价

辛渊蓉¹, 张驰¹, 戴金通¹, 杨凯伦³, 何海冰⁴^,^*(), 刘宏飞¹^,²^,^*()

^1. 江苏大学药学院, 江苏镇江 212013
^2. 江门宏晓生物医药科技有限公司, 广东江门 529000
^3. 天津中医药大学, 天津 301617
^4. 江苏海之宏生物医药有限公司, 江苏南通 226001

收稿日期:2025-09-25 修回日期:2025-10-21 接受日期:2025-11-06 出版日期:2026-01-31 发布日期:2026-01-31
通讯作者: 何海冰, 刘宏飞

Preparation and evaluation of cefditoren bioadhesive sustained-release dry suspension in vitro and in vivo studies

Yuanrong Xin¹, Chi Zhang¹, Jintong Dai¹, Kailun Yang³, Haibing He⁴^,^*(), Hongfei Liu¹^,²^,^*()

¹ College of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China
² Jiangmen Hongxiao Biomedical Co., Ltd, Jiangmen 529000, Guangdong, China
³ Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
⁴ Jiangsu Haizhihong Biomedical Co., Ltd, Nantong 226001, Jiangsu, China

Received:2025-09-25 Revised:2025-10-21 Accepted:2025-11-06 Online:2026-01-31 Published:2026-01-31
Contact: Haibing He, Hongfei Liu
Supported by:
The 2023 Nantong Jianghai Talents Project, 2023 Nantong Social Livelihood Science and Technology Plan, 2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research Institute, Wuyi University Scientific Research Project (Grant No. 2023AL001), and the Innovation and Entrepreneurship Project for Returned Overseas Students in Jiangmen.

摘要/Abstract

摘要：

本研究以头孢妥仑的钠盐头孢妥仑钠作为模型药物, 以考来烯胺阴离子交换树脂作为关键性药物载体, 制备了头孢妥仑钠的药物树脂复合物, 采用扫描电镜、傅里叶变换红外光谱仪、差示扫描量热仪等分析手段对头孢妥仑钠与考来烯胺树脂之间的结合方式进行了表征。采用乳化溶剂挥发法包衣技术制备了具有生物黏附性能和缓释效果明显的包衣树脂微囊, 并对其相关质量指标进行了研究。自制制剂7天时的泄漏量仅为0.07%, 6个月时混悬剂中药物含量为94.59%。体内药代动力学参数显示, 头孢妥仑钠原料药溶液和自制干混悬剂的T_max分别为2 h和3 h, t_1/2 分别为4 h和12.44 h, C_max分别为4.82和3.99 μg/mL, AUC_{0-24 h}分别为30.281和50.868 μg·h/mL。与头孢妥仑钠原料药溶液相比, 自制的干混悬剂t_1/2和T_max更长, C_max更低, 生物利用度好。

关键词: 头孢妥仑, 离子交换树脂, 缓释干混悬剂

Abstract:

In the present study, cefditoren sodium (CT-Na), the sodium salt form of cefditoren (CT), was selected as the model compound, and cholestyramine resin was employed as the drug carrier to formulate CT-Na-resin complexes. The interaction mechanism between CT-Na and cholestyramine resin was elucidated using scanning electron microscopy (SEM), fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Bioadhesive, sustained-release microcapsules were subsequently developed via an emulsification–solvent evaporation technique. Comprehensive characterization of the formulation was conducted, with key quality indices systematically evaluated. Notably, the formulation exhibited minimal leakage (0.07%) after 7 d of storage and retained 94.59% of its drug content over a 6-month period. Pharmacokinetic studies comparing the CT-Na active pharmaceutical ingredient (API) solution and the self-developed dry suspension revealed a marked extension in drug release for the latter. The dry suspension displayed a delayed T_max (3 h vs. 2 h), an extended half-life (t_1/2) (12.44 h vs. 4 h), and a moderately reduced peak concentration (C_max) (3.99 μg/mL vs. 4.82 μg/mL), while achieving a significantly higher overall drug exposure (AUC_{0–24 h}: 50.868 μg·h/mL vs. 30.281 μg·h/mL). These findings indicated that relative to the API solution, the optimized dry suspension provided sustained drug release with improved bioavailability.

Key words: Cefditoren, Ion-exchange resin, Sustained-release dry suspension

Supporting:

辛渊蓉, 张驰, 戴金通, 杨凯伦, 何海冰, 刘宏飞. 头孢妥仑生物黏附缓释干混悬剂的制备及体内外评价[J]. 中国药学(英文版), 2026, 35(1): 54-70.

Yuanrong Xin, Chi Zhang, Jintong Dai, Kailun Yang, Haibing He, Hongfei Liu. Preparation and evaluation of cefditoren bioadhesive sustained-release dry suspension in vitro and in vivo studies[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(1): 54-70.

图/表 17

Figure 1. Schematic diagram of the separation force experiment.

Figure 2. Schematic diagram of shear force experiment.

Figure 3. Effect of rotational speed (a), drug-resin ratio (b), and drug concentration (c) on the preparation of CT-Na–DRC by static method.

Figure 4. SEM morphology comparison of blank resin (left) and CT-Na–DRC (right).

Figure 5. FTIR map of resin, CT-Na, physical mixture, and CT-Na–DRC.

Figure 6. DSC thermograms of resin, CT-Na, physical mixture, and CT-Na–DRC.

Table 1. Effects of different coating prescriptions on retention test and sustained-release weighted score of CT-Na–CM in isolated animals (n = 3).

Table 2. Similarity analysis of different coating prescriptions on the in vitro release of CT-Na–CM.

Figure 7. Effects of the type of sustained-release coating material (a), different ratios of coating materials (b), the concentration of coating material (c), and different dosages of plasticizer (d) on the release of CT-Na–CM.

Figure 8. SEM morphology comparison of CT-Na–DRC (left) and CT-Na–CM (right).

Figure 9. Particle size distribution of CT-Na–CM.

Figure 10. The results of CT-Na–CM detachment force measurement.

Figure 11. The results of CT-Na–CM shearing stress measurement.

Figure 12. The result of in vivo adhesion assay of CT-Na–CM in rats.

Table 3. Room temperature retention test data for self-made CT-Na dry suspension.

Table 4. Pharmacokinetic parameters of CT-Na API and self-prepared CT-Na bioadhesive sustained-release suspension (n = 6).

Figure 13. In vivo curve of drug time of CT-Na API solution, self-made CT-Na sustained-release suspension (n = 6).

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头孢妥仑生物黏附缓释干混悬剂的制备及体内外评价

Preparation and evaluation of cefditoren bioadhesive sustained-release dry suspension in vitro and in vivo studies

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