Optimization of Calcium Carbonate and Vitamin D3 Chewable Tablets Formulation Optimization of Calcium Carbonate D3 Chewable Tablet Formulation Based on Reducing Side Effects of Constipation
LI Mingdan, LIU Li, XIE Yuyuan, et al
Hunan Research Center for Safety Evaluation of Drugs, Hunan Key Laboratory for Pharmacodynamics and Safety Evaluation of New Drugs, Changsha Pediatric Drug Research Technology Innovation Center,Changsha Hunan 410329
Abstract：【Objective】To investigate the optimal method of calcium carbonate D3 chewable tablet formulation based on reducing side effects of constipation. 【Methods】The effects of different excipients on small intestine movement of mice were investigated by literature, and 5 commercially available products composed of different excipients were selected. According to the excipients composition of commercially available products, 2 kinds of finished products were made in the laboratory, and the optimal excipients composition was selected by mouse small intestine movement test. ICR mice were randomly divided into 8 groups according to body weight, namely blank control group, 401 self-made group, 601 self-made group, marketed product 1, 2, 3, 4 group and Jinbei commercial product group, with 20 mice (half male and half female) in each group. Single administration test (once administration) and repeated administration test (30 days administration) were conducted respectively. The dose of mice in each administration group was 130 mg/kg (measured by calcium), and the corresponding volume of pure water was given to the blank control group. The general clinical manifestations and fecal characteristics of mice were observed every day during the experiment. The fecal properties of mice in each experimental group were observed and photographed every week in the repeated administration test groups, and the fecal weight was measured within 6 hours. Intestinal propulsion test was performed after the last administration in both single administration test and repeated administration test to calculate the intestinal ink propulsion rate of mice. 【Results】Single administration of Calcium carbonate and vitamin D3 chewable tablets composed of different excipients had no significant effect on small intestinal propulsion rate in mice. After repeated administration for 30 days, compared with the blank control group, fecal dryness was observed in mice in 601 self-made group, marketed product 1, 2, 3, 4 group, and the ink advancing rate was significantly reduced(P<0.05). The fecal weight of mice treated with 3 weeks and 4 weeks in 601 self-made group, marketed product 3, 4 group, and the fecal weight of mice treated with 4 weeks in marketed product 1, 2 group were significantly reduced(P<0.05); There were no significant effects on fecal traits, intestinal propulsion rate and fecal weight in 401 self-made group and Jinbei brand market group. 【Conclusion】Calcium carbonate and vitamin D3 chewable tablets containing defecation promoting components can reduce constipation side effects caused by repeated administration, and excipients with different defecation promoting mechanisms can play a synergistic role. Through comparison in this study, Jinbei brand Calcium carbonate and vitamin D3 chewable tablets (Ⅱ) (patent No.ZL 2021 1 0357997.6), which is owned by Zhejiang Huanling Pharmaceutical Technology Co., Ltd., has the best prescription process. It can effectively reduce the side effect of constipation caused by repeated administration.
李明丹, 刘理, 谢宇圆, 朱恒, 陈志. 基于降低便秘副作用的碳酸钙D3咀嚼片制剂处方优化的研究*[J]. 医学临床研究, 2024, 41(7): 964-968.
LI Mingdan, LIU Li, XIE Yuyuan, et al. Optimization of Calcium Carbonate and Vitamin D3 Chewable Tablets Formulation Optimization of Calcium Carbonate D3 Chewable Tablet Formulation Based on Reducing Side Effects of Constipation. JOURNAL OF CLINICAL RESEARCH, 2024, 41(7): 964-968.
2024, Vol. 41 
