Zn2+-Ca2+二元离子调控HPMC肠溶空心胶囊性能

doi:10.16085/j.issn.1000-6613.2024-1690

化工进展 ›› 2025, Vol. 44 ›› Issue (4): 2250-2257.DOI: 10.16085/j.issn.1000-6613.2024-1690

Zn²⁺-Ca²⁺二元离子调控HPMC肠溶空心胶囊性能

喻喜华¹^,²(), 何楚琪³^,⁴, 许福春¹^,², 石贞香¹^,², 刘振宇³, 肖美添³^,⁴()

^1.国药控股星鲨制药(厦门)有限公司，福建厦门 361021
^2.厦门市母婴健康营养产品重点实验室，福建厦门 361026
^3.华侨大学化工学院，福建厦门 361021
^4.厦门海洋生物资源综合利用工程技术研究中心，福建厦门 361021

收稿日期:2024-10-22 修回日期:2024-12-11 出版日期:2025-04-25 发布日期:2025-05-07
通讯作者: 肖美添
作者简介:喻喜华（1985—），男，硕士，高级工程师，研究方向为药物制剂。E-mail：yuxihua100@163.com。
基金资助:
国家自然科学基金(22078120);福建省高校产学合作项目(2024Y4007)

Regulation of the properties of HPMC-based enteric hard capsule by Zn²⁺-Ca²⁺ binary ions

YU Xihua¹^,²(), HE Chuqi³^,⁴, XU Fuchun¹^,², SHI Zhenxiang¹^,², LIU Zhenyu³, XIAO Meitian³^,⁴()

^1.Sinopharm Xingsha Pharmaceuticals (XIAMEN) Co. , Ltd. , Xiamen 361026, Fujian, China
^2.Xiamen Key Laboratory of Maternal and Infant Health and Nutrition Products, Xiamen 361026, Fujian, China
^3.College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian, China
^4.Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen 361021, Fujian, China

Received:2024-10-22 Revised:2024-12-11 Online:2025-04-25 Published:2025-05-07
Contact: XIAO Meitian

摘要/Abstract

摘要：

针对结构致密性不足的问题，采用乳酸锌和氯化钙复合离子溶液对海藻酸钠基囊胚进行二元离子交联反应，制备致密性好且力学性能优良的HPMC肠溶空心胶囊。通过FTIR、XRD、SEM、EDS、力学性能试验等对胶囊膜进行结构表征和性能测试，并探究了复合离子溶液的Zn²⁺-Ca²⁺摩尔比对HPMC肠溶空心胶囊微观形貌及理化性能的影响。研究表明，添加一定量的乳酸锌能够提高胶囊结构的致密性，但当Zn²⁺-Ca²⁺摩尔比大于1∶4时，经交联后胶囊膜中锌元素和钙元素的总含量降低，剩余钠元素含量增大，即海藻酸钠与离子的交联率有所降低，这不利于胶囊膜的力学性能和胶囊的成型性指标。通过结构表征及理化性能评估，确定n(Zn²⁺)∶n(Ca²⁺)=1∶4时为胶囊交联反应的最佳比例，此时胶囊力学性能与致密性较优，拉伸强度达50.12MPa，断裂伸长率为2.0%，水蒸气透过率为2.75×10^-11g/(m·s·Pa)，成囊率达94%，松紧度合格率为96%，脆碎度合格率为96%。由最佳交联比例制得的HPMC肠溶空心胶囊产品表观质量良好，各项指标均符合《中国药典》（2020年版）和相关行业标准。

关键词: 凝胶, 乳酸锌, 氯化钙, 扩散, 肠溶空心胶囊

Abstract:

In order to solve the problem of insufficient structural compactness, the composite ionic solution of zinc lactate and calcium chloride was used to perform binary ionic cross-linking reaction on sodium alginate-based capsules to prepare HPMC-based enteric hard capsules with good compactness and excellent mechanical properties. Structural characterization and performance testing of the capsule membranes were conducted using FTIR, XRD, SEM, EDS, and mechanical property tests. The influence of the Zn²⁺-Ca²⁺ molar ratio in the composite ionic solution on the microstructure and physicochemical properties of the HPMC-based enteric hard capsules was investigated. The study demonstrated that adding a certain amount of zinc lactate enhanced the structural density of the capsules. However, when the Zn²⁺-Ca²⁺ molar ratio exceeded 1∶4, an increase in the proportion of Zn²⁺ led to a decrease in the total content of zinc and calcium in the capsule membranes, along with an increase in the remaining sodium content. This resulted in a reduced cross-linking rate and cross-linking degree between sodium alginate and the ions, ultimately lowering the tensile strength and affecting the capsule’s forming characteristics. Through structural characterization and physicochemical performance evaluation, it was determined that the optimal ratio for the capsule cross-linking reaction was n(Zn²⁺)∶n(Ca²⁺)=1∶4. At this ratio, the capsules exhibited superior mechanical properties and density, with a tensile strength of 50.12MPa, a fracture elongation of 2.0%, a water vapor permeability of 2.75×10⁻¹¹g/(m·s·Pa), a capsule formation rate of 94%, a pass rate of 96% for tightness, and a pass rate of 96% for brittleness. Finally, the HPMC enteric hollow capsule products obtained at the optimal cross-linking ratio demonstrated good appearance quality, with all indicators meeting the standards outlined in the “Pharmacopoeia of the People’s Republic of China”(2020 edition) and relevant industry standards.

Key words: gels, zinc lactate, calcium chloride, diffusion, enteric hard capsule

中图分类号:

TQ460.4

喻喜华, 何楚琪, 许福春, 石贞香, 刘振宇, 肖美添. Zn²⁺-Ca²⁺二元离子调控HPMC肠溶空心胶囊性能[J]. 化工进展, 2025, 44(4): 2250-2257.

YU Xihua, HE Chuqi, XU Fuchun, SHI Zhenxiang, LIU Zhenyu, XIAO Meitian. Regulation of the properties of HPMC-based enteric hard capsule by Zn²⁺-Ca²⁺ binary ions[J]. Chemical Industry and Engineering Progress, 2025, 44(4): 2250-2257.

图/表 9

图 1 不同摩尔比离子溶液交联制备胶囊的傅里叶红外光谱图

图 2 不同摩尔比例离子溶液交联制备胶囊的X射线衍射图

图 3 不同摩尔比例离子溶液交联制备胶囊的表面能量色散X射线谱及元素分布(a)、(a')、(a") 表面形貌；(b)、(b')、(b") 钠元素分布；(c)、(c')、(c") 氯元素分布；(d)、(d')、(d") 钙元素分布；(e)、(e')、(e") 锌元素分布；(f)、(f')、(f") 元素信号强度

图 4 不同摩尔比离子溶液交联制备胶囊的截面能量色散X射线谱及元素分布(a)、(a') 截面形貌和各元素分布；(b)、(b') 沿截面纵向各元素分布；(c)、(c') 钙元素分布；(d)、(d') 锌元素分布；(e)、(e') 钠元素分布；(f)、(f') 截面元素信号强度

表 1 不同摩尔比离子溶液交联制备胶囊的截面能量色散X射线谱的元素质量分数

元素	元素质量分数/%		钠、钙、锌元素归一化质量分数/%
元素	1∶4	4∶1	1∶4	4∶1
C	69.52	70.86	—	—
O	27.19	27.27	—	—
Na	0.86	0.80	0.51	0.69
Cl	1.14	0.20	—	—
K	0.48	0.51	—	—
Ca	0.73	0.06	0.44	0.05
Zn	0.09	0.30	0.05	0.26

图 5 不同Zn2+-Ca2+离子配比对胶囊力学性能影响

图 6 不同Zn2+-Ca2+离子配比对胶囊水蒸气透过率影响

表 2 不同Zn2+-Ca2+离子配比对胶囊成型性指标的影响

n(Zn²⁺)∶n(Ca²⁺)	成囊率/%	松紧度合格率/%	脆碎度合格率/%
5∶0	93	89	95
4∶1	94	92	96
3∶2	94	93	94
1∶1	94	96	93
2∶3	93	95	95
1∶4	94	96	96
0∶5	91	92	92

图 7 最优Zn2+-Ca2+摩尔比例交联制备的HPMC肠溶空心胶囊

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Zn²⁺-Ca²⁺二元离子调控HPMC肠溶空心胶囊性能

Regulation of the properties of HPMC-based enteric hard capsule by Zn²⁺-Ca²⁺ binary ions

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