The effects of fatty acids in propylene glycol on the percutaneous absorption of alendronate across the excised hairless mouse skin

Abstract

The effects of fatty acids at various concentrations in propylene glycol (PG) on the in vitro permeation of alendronate from solution formulations and formulated pressure-sensitive adhesive (PSA) transdermal delivery systems through excised hairless mouse skin were investigated. Caprylic acid, capric acid, lauric acid, oleic acid and linoleic acid at concentrations of 3, 6 and 10% were employed as a fatty acid. The highest maximum permeation flux was obtained with 3% capric acid in PG followed by 6% capric acid and 3% oleic acid from solution formulations; the enhancement factor by the addition of 3% capric acid to PG was 20.5 compared to PG alone. On the contrary, from PSA transdermal delivery systems, the highest enhancement factor of 2.9 was attained with 6% caprylic acid in PG compared to PG alone. The maximum permeation flux and lag time from PSA transdermal delivery systems by the addition of 6% caprylic acid to PG were 195.68 ± 26.6 ng/cm2/h and 0.6 ± 0.3 h whereas PG without fatty acids showed 67.3 ± 5.8 ng/cm2/h and 0.5 ± 0.4 h, respectively. The PSA transdermal delivery systems initially provided very high permeation rate followed by a gradual decrease regardless of the fatty acids. The highest release rate was also obtained with the formulation containing 6% caprylic acid in PG although release rates were not matched with permeation rates perfectly. In conclusion, for effective transdermal delivery system of alendronate, 6% caprylic acid in PG could be employed. © 2008 Elsevier B.V. All rights reserved.