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Effects of amines on percutaneous absorption of alendronate
1College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-Dong Seodaemun-Gu, Seoul, Korea.
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.
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