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

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