Effect of antioxidants and anti-irritants on the stability, skin irritation and penetration capacity of captopril gel.
The effects of antioxidants and chelating agent on the stability of captopril in aqueous and semisolid were determined in this study. Then the influence of the combination of additives including antioxidants, anti-irritants and penetration enhancer on stability, skin irritation and penetration capacity of captopril in semisolid dosage form was investigated. In the stability study, the degradation of captopril followed the first-order kinetic. The chelating agent EDTA showed a potent stability effect and obviously increased the shelf-life up to 14-fold that of control gel. The anti-irritants such as clobetasol and diphenhydramine had potent inhibition irritation activity and the effect was not retarded by the addition of EDTA. Moreover, the captopril gel containing penetration enhancer, anti-irritants and chelating agent had a higher penetration capacity and the minimum therapeutic concentration could be obtained by applying about 13.24 cm(2) of administered area, indicating that the formulation can possibly be developed for a transdermal drug delivery system.
Huang
Yaw-Bin
YB
College of Pharmacy, Kaohsiung Medical University, 100 Shih-Chen 1st R.D., Kaohsiung 807, Taiwan, ROC.
Tsai
Yi-Hung
YH
Chang
Jui-Sheng
JS
Liu
Jian Chen
JC
Tsai
Ming-Jun
MJ
Wu
Pao-Chu
PC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D002216:Captopril / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004355:Drug Stability; D004890:Erythema / Q000139:chemically induced*; D005782:Gels; D011817:Rabbits; D012869:Skin Absorption / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D005782:Gels; D002216:Captopril