Communication: Matrix type transdermal drug delivery systems of metoprolol tartrate: skin toxicity and <i>in vivo</i> characterization

Abstract

Transdermal drug delivery systems (TDDS) of metoprolol were previously fabricated and evaluated in vitro. The TDDS was composed of polymers Eudragit RL 100 and polyvinyl pyrrolidone K-30 in 8:2, 4:6, 6:4 and 2:8 fractions in formulations MT-1, MT-2 MT-3 and MT-4, respectively. All formulations carried 10% w/w of drug; metoprolol tartrate, 5% w/w of plasticizer; polyethylene glycol 400 and 5% w/w of penetration enhancer; dimethylsulfoxide (based on total polymers weight). The influence of the developed patch on the blood pressure of experimental hypertensive rats and its skin irritation potential is presented in this report. The study was carried out in thirty six male albino rats. They were divided into six groups of six animals each. Group A received no treatment (control). Group B was administered with methylprednisolone acetate (MPA) (20 mg/kg/week) for two weeks (toxic control). Group C, D, E and F received MPA followed by MT-1, MT-2, MT-3 and MT-4 TDDS, respectively (treatment groups). The blood pressure of rats was measured using a non-invasive rat BP instrument based on cuff-tail technique. The statistical analysis was performed using GraphPad Instat 3 software. All the treatment groups showed significant (P < 0.05) and constant fall in BP up to 48 h. Formulation MT-4 was found to be most effective with 42.66% reduction in BP. Histopathological reports ruled out possibility of any skin irritation on patch application in rabbits.

Keywords: transdermal, metoprolol, in vivo characterization, hypertension, skin toxicity

Ethiopian Pharmaceutical Journal, vol. 22 (2004): 53-60