Study On Glibenclamide Latex

Glibenclamide is a potent,second generation oral sulfonylurea hypoglycemic agent widely used in the treatment of non insulin-dependent diabetic patients.However,it has been associated with severe and sometimes fatal hypoglycemia,liver functional damage,gastrointestinal irritation and skin sensitization after oral therapy.In order to reduce the adverse effects after oral administration,the glibenclamide emulgel was formulated and evaluated in vitro and in vivo.The effects of ion pairing and penetration enhancers on the permeation of glibenclamide through rat skin from vehicle 1(isopropyl myristate:ethanol,3:7)and vehicle 2(isopropyl myristate:ethanol,7:3)were investigated using side-by-side diffusion cells.As counter ions, diethylamine,triethylamine,ethanolamine,diethanolamine and triethanolamine were used.The steady-state flux of glibenclamide markedly increased in the presence of counter ions.For vehicle 1,the highest flux was observed with diethylamine and triethylamine.However,for vehicle 2,ethanolamine provided the highest enhancement in glibenclamide flux.It is possible to enhance the flux of glibenclamide by using an ion pair approach.Moreover,the extent of enhancement possibly depends on the alkalinity,molecular weight,structure of the counter ions and the dielectric constant of the donor solution.In addition,N-methyl-2-pyrrolidone,azone, menthol and oleic acid were employed as penetration enhancers.All the penetration enhancers studied increased the flux of glibenclamide compared to the control.For vehicle 1,menthol exhibited the greatest enhancing effect.For vehicle 2,menthol and N-methyl-2-pyrrolidone showed the greatest enhancing effect.Moreover,there is an inverse relationship between the lipophilicity of enhancers and their enhancing activity.For both vehicles,diethylamine showed higher enhancing activities.So,the influence of penetration enhancers in combination with diethylamine on the permeation of glibenclamide was evaluated.No statistically significant synergistic effect was observed when diethylamine was combined with enhancers.The effects of different concentrations of diethylamine on the permeation of glibenclamide from emulgel through rat skin were investigated using vertical diffusion cells.The influence of various organic amines and penetration enhancers on the permeation of glibenclamide from emulgel was also investigated.In addition,the glibenclamide emulgel was evaluated for its hypoglycemic activity in normal rats.The highest steady-state flux was observed when 0.70% diethylamine and 3%azone were added.The glibenclamide emulgel produced a significant reduction in blood glucose levels compared to the control(P＜0.01).The glibenclamide emulgel had significant hypoglycemic effect,so it may be a promising candidate for the treatment of diabetes.