The effect of ultrasound and chemical penetration enhancers on transcutaneous flux of penbutolol sulfate across split-thickness porcine skin was investigated. Penbutolol sulfate is a potent, noncardioselective beta-blocker, which is used for the management of hypertension. The drug is one of the most lipid soluble of the β-adrenoceptor antagonists used clinically. It has an n-octanol/pH 7.4 buffer partition coefficient of 179 compared to a value of 22 for propranolol. The amount of penbutolol sulfate transported across the skin is low. In this project, we studied the effect of sonophoresis and chemical penetration enhancers on transdermal delivery of penbutolol sulfate. Low-frequency sonophoresis at a frequency of 20 kHz increased transcutaneous flux of penbutolol sulfate by 3.5-fold (27.37 ± μg cm-2 h-1) compared to passive delivery (7.82 ± 1.72 μg cm-2 h-1). We also investigated the effect of 50% ethanol, 1% limonene and 2% isopropyl myristate (IPM) on transcutaneous permeation of penbutolol sulfate. IPM, ethanol and limonene at the concentration of 1%, 50% and 2%, respectively, increased the steady-state flux values of penbutolol sulfate 2.2- (17.07 ± 3.24 μg cm-2 h-1), 2.6 - (19.40 ± 6.40 μg cm-2 h-1) and 3.4-times (26.38 ± 5.01 μg cm-2 h-1) compared to passive delivery (7.76 ± 2.9 μg cm-2 h-1). The results demonstrate that although there were slight increases in flux values, ultrasound, ethanol, limonene and IPM did not significantly enhance the transdermal delivery of penbutolol sulfate. Future studies will examine ways of optimizing sonophoretic and chemical enhancer parameters to achieve flux enhancement.
Keywords: Drug delivery; penbutolol sulfate; penetration enhancers; sonophoresis; transdermal.