Effect of antioxidants on captopril floating matrices

Abstract

Stability of captopril in a controlled release formulation has been a challenge for some time. The sustained release of captopril from floating matrices has been studied varying the antioxidant load, the sodium bicarbonate proportion and the compaction pressure. Although in many cases the effect of compaction pressure remains hidden, actual results show that matrices compacted at 55 MPa have smaller density and float in the dissolution medium while those compacted at 165 MPa float only adding sodium bicarbonate. The increase of compaction pressure reduces the hydration volume and increases the time necessary to attain its maximum. These changes are attributed to lower matrix porosity and to the consequent diminution of water and drug transport. Increasing ascorbic acid proportions increase the matrix hydration volume and the drug released. The use of sodium ascorbate and the substitution of 15% polymer with sodium bicarbonate reduce the matrix hydration volume, shorten the matrix hydration process and increase the drug released. This is attributed to carbon dioxide bubbles that decrease the matrix coherence and expand the matrix volume, facilitating drug dissolution and only a limited further matrix expansion. The antioxidant protection provided by sodium ascorbate was lesser of that of ascorbic acid because of greater molecular mass and lesser release rate.

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

“…3 In addition, Cap undergoes oxidation at its thiol group to yield captopril disulfide (Di-Cap, Scheme 1) in aqueous solution. 4 Approaches to utilize cyclodextrin, layered double hydroxides, and polymer-mesoporous silica to slow down the release rate of captopril have been reported. 5−8 We consider that the overhigh maximum plasma concentration of Cap could be reduced simply by the formation of coordination polymers of metal ions with Cap, as Cap contains three potential donor groups (thiol, carboxyl, and amide) which might act as a linker to form coordination polymers with metal ions.…”