Effect of novel terpenes penetration enhancer on in-vitro percutaneous penetration of propranolol hydrochloride hydrogel / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of different novel terpenes penetration enhancers and their combinations on percutaneous absorption of propranolol hydrochloride hydrogel and screen the best penetration enhancers so as to increase the cumulative permeation quantity in the target site. METHODS: The percutaneous permeation experiment was carried out with modified Franz-type diffusion cell with isolated piglet skin as the barrier. The effects of the types, concentrations, and combinations of penetration enhancers on the transdermal penetration of propranolol hydrochloride hydrogel were compared using cumulative permeation quantity (Q) and enhancing rate (ER) as indexes. RESULTS: The effectiveness of terpenes was found to be the optimal at concentration of 3% in the following order; farnesol > L-menthol > nerolidol > tetrahydrogeraniol > 1, 4-cineole≈geraniol > limonene > anethole > borneol > negative control > dipotassium glycyrrhizic acid. The release profiles from the hydrogel formulations obeyed zero-order kinetics. Farnesol, L-menthol, and nerolidol effectively promoted the percutaneous penetration of propranolol hydrochloride over the concentration range of 1% - 5%. The enhancement ratio was the highest at 3% and decreased if the concentration increased to 5%. Significant synergism was observed when the enhancers were used in combination (P < 0.05), while there was an antagonistic effect when 3% farnesol or 3% L-menthol was combined with propylene glycol (P < 0.05). CONCLUSION: The percutaneous absorption of propranolol hydrochloride is increased by the terpenes enhancers and reached the peak value with 3% farnesol plus 10% isopropanol. These findings provide a basis for the further transdermal delivery studies of propranolol hydrochloride.