Complex compounds of mesalazine with cyclodextrins and the prospect of their application in the ulcer disease treatment

Abstract

Mesalazine is highly effective in the treatment of ulcerative colitis and Crohn’s disease. However, in view of the fact that this compound is easily absorbed in the upper small intestine and cannot reach the large intestine at a therapeutic concentration, it is relevant to enclose it in the cavity of cyclodextrins through the formation of inclusion complexes of the “guest–host” type. Mesalazine complexation with α-, β-, γ- cyclodextrins was studied by spectrophotometric method in aqueous solutions. We established that the composition of the resulting complexes is 1:1. In the temperature range 296 - 321 K, the stability constants are calculated, and the thermodynamic parameters of complex formation are determined. We developed a technique for the synthesis of complexes, and a prototype, and studied its antiulcer activity. The authors established that the complex of mesalazine with β- cyclodextrin has a more pronounced antiulcer activity compared to the original substances, and approximately the same action as the reference drug (Omez). However, the amount of mesalazine in the complex was only 12% wt., the remaining 88% wt. account for β- cyclodextrin. The results obtained indicate the possibility of complex formation between mesalazine and α-, β-, γ- cyclodextrins. The resulting complex compounds can become the basis of new anti-inflammatory and antiulcer drugs.