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.

Aplicação de resina poliuretânica derivada do óleo de mamona em formas farmacêuticas gastrorretentivas de liberação controlada

“…Drug instability, regardless its nature, can also be a reason to justify gastric retention. GRDDS can benefit substances with physicochemical instability, like captopril that degrade in alkaline medium (JIMÉNEZ-MARTÍNEZ et al, 2010); substances with biochemical instability, like cefpodoxime proxetil that undergo enzymatic degradation (KAKUMANU et al, 2006); and substances with biological instability, like when there are unabsorbed forms of amoxicillin (HORWITZ et al, 2011) and cefuroxime (JAMMULA et al, 2015) in the colon, causing bacterial resistance and colitis, respectively.…”