Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance

• Published in: Pharmacology research & perspectives Vol. 12; no. 2; pp. e1186 - n/a
• Main Authors: Lv, Zhong, Luo, Qian‐Dong, Tang, Zhang‐Yong, Lv, Xiao‐Hu, Wu, Tao, Huang, Ling‐Kai, Tang, Can
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc; Wiley
• Subjects: Administration, Oral; Alkalinity; Animals; Bioavailability; Biotechnology; Caco-2 Cells; Cancer; Caprylates; Caustic soda; Chromatography; Cytotoxicity; Diabetes; Diabetic nephropathy; enhancing absorption; Enzymes; enzyme‐linked immunosorbent assay; Experiments; Humans; Hydrochloric acid; Kallikreins; Original; pancreatic kininogenase; Patient compliance; Permeability; Pharmaceuticals; pharmacokinetics; Rats; Raw materials; Salcaprozate sodium; Small intestine; Sodium; Suctioning; pharmacokinetics; Caco‐2 cells; pancreatic kininogenase; enhancing absorption; Salcaprozate sodium; enzyme‐linked immunosorbent assay
• ISSN: 2052-1707; 2052-1707
• DOI: 10.1002/prp2.1186

We conducted pharmacokinetic research wherein salcaprozate sodium (SNAC) was utilized as a penetration enhancer by incorporating it into pancreatic kininogenase (PK) to improve the bioavailability of pancreatic kininogenase enteric‐coated tablets. We conducted in vitro studies on PK using the Caco‐2 cell model and quantified PK levels using the enzyme‐linked immunosorbent assay (ELISA) method. We conducted methodological verification by blending SNAC and PK powders into enteric‐coated capsules, and studied the pharmacokinetic characteristics. Based on the PK transport assay, the cumulative permeation rates of the test group that employed a SNAC to PK ratio of 32:1, 16:1, 8:1, 4:1, and 2:1 were 13.574%, 7.597%, 10.653%, 3.755%, and 2.523%, respectively. We conducted a uniformity test on the powder that contained a blend of SNAC and PK. The relative standard deviations (RSDs) for both the power containing SNAC and the power not containing SNAC were less than 10%. Based on the methodological verification, in vivo pharmacokinetic study of PK met the experimental requirements. As indicated by the results of in vivo pharmacokinetic research on rats, the test group (This group used SNAC) had a PK AUC0–12 h of 5679.747 ng/L*h and t1/2 of 4.569 h, while the control group (This group did not use SNAC) had a PK AUC0–12 h of 4639.665 ng/L*h and t1/2 of 3.13 h. This study has established a low‐cost, environmentally friendly, and safe SNAC synthesis route with high process yield suitable for industrial production. SNAC demonstrates an absorption‐enhancing effect on PK, and the optimal ratio of SNAC to PK is determined to be 32:1. Research flow chart.