New Approach to Reduce the Overhigh Plasma Concentration of Captopril by the Formation of Zinc Coordination Polymer

Abstract

Captopril is an antihypertension drug, it has side effects of vertigo, headache, and functional gastrointestinal disorders due to its overhigh plasma concentration. In addition, captopril undergoes oxidation at its thiol to yield captopril disulfide. In order to reduce its release rate and increase its oxidation stability, coordination polymer of captopril with zinc ion was prepared and its structure was determined by single crystal X-ray diffraction. The results of solubility measurements indicate that the apparent solubility and intrinsic dissolution rate of captopril can be dramatically decreased after the formation of coordination polymer. Pharmacokinetic studies in rats reveal that the plasma concentration of captopril can be reduced by the formation of zinc coordination polymer, with maximum plasma concentration reduced from 2.53 μg/mL for captopril to 0.99 μg/mL for the zinc coordination polymer. Moreover, the oxidation stability of captopril is simultaneously improved by the formation of zinc coor...