Effects of amines on percutaneous absorption of alendronate

Abstract

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/cm2/h, respectively. The maximum permeation flux of 1.79 ± 0.28 μg/cm2/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/cm2/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.