Percutaneous absorption of bromhexine in rats

The percutaneous absorption of bromhexine (BH), an expectorant drug, through rat skin was examined in vitro and in vivo. BH in free base form penetrated better than the hydrochloride through the skin. When the in vitro penetration of BH was compared using Plastibase, macrogol and sucrose ester of fatty acid F-160 (DK-ester) formulations, the DK-ester formulation showed the best penetration of BH of the three. The addition of Azone (3%) or lauric acid (BH: lauric acid molar ratio, 1:1) considerably increased BH penetration to a relatively large penetration rate. The plasma levels of BH after in vivo application of the DK-ester formulation with Azone or lauric acid (0.6 g/3.8 cm2) were also higher than those after the formulation without an enhancer, and a constant plasma level (20-50 ng/ml) was obtained during the application for 48 h. However, the bioavailability was low, 2.5 and 2.7% respectively. When the amount of BH remaining in DK-ester ointment and the skin after an 18-h application was measured, the BH content in the ointment was 88.6 +/- 8.0% for the formulation without Azone and 93.7 +/- 6.9% for that with Azone. The low penetration and low bioavailability observed will thus be due to the high drug retention of the base.