Effects of amines on percutaneous absorption of alendronate.

OBJECTIVE

The aim of this study was to examine the effects of amines on the permeation of alendronate using solution formulations and pressure-sensitive adhesive (PSA) transdermal delivery systems (TDS).

MATERIALS AND METHODS

Monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), diethylamine (DEYA), and triethylamine (TEYA) at concentrations of 3, 6, and 10% were added to propylene glycol (PG) containing 6% caprylic acid. In vitro and in vivo experiments were conducted using alendronate solution and PSA TDS formulations.

RESULTS

When using saturated solution formulations, 3% TEA and 10% DEYA showed high permeation rates of 8.20 ± 0.80 and 7.87 ± 0.18 μg/cm(2)/h, respectively. The maximum permeation flux of 1.79 ± 0.28 μg/cm(2)/h from 1 mg/ml solution was obtained with the addition of 10% DEYA followed by the addition of 10% TEYA (1.72 ± 0.72 μg/cm(2)/h). The highest enhancement factor of 1.86 was obtained with alendronate PSA TDS containing 10% MEA compared with no amine. In the in vivo study, the amount remaining to be excreted (ARE) at time 0 (Ae(∞)) and ARE at time t [Ae(t)] differed between TDS and oral delivery significantly (P < 0.01). The TDS containing 10% MEA showed the highest Ae(∞) (19.5 ± 6.93 μg), which was 2.7- and 2.2-fold, compared with oral and no amine administration, respectively.

CONCLUSION

Based on the results, TDS with 10% MEA in PG containing 6% caprylic acid could be a good candidate for the alendronate TDS.