Development of a Novel Transdermal Patch of Alendronate, a Nitrogen-Containing Bisphosphonate, for the Treatment of Osteoporosis

作者：Kusamori Kosuke; Katsumi Hidemasa; Abe Mari; Ueda Asuka; Sakai Ryota; Hayashi Rie; Hirai Yuka; Quan Ying Shu; Kamiyama Fumio; Sakane Toshiyasu; Yamamoto Akira^*

来源：Journal of Bone and Mineral Research, 2010, 25(12): 2306-2315.

DOI：10.1002/jbmr.147

• BISPHOSPHONATES
• OSTEOPOROSIS
• TRANSDERMAL
• DELIVERY
• SKIN

Bisphosphonates are widely used for the treatment and prevention of bone diseases, including Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis In this study, we developed a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of bone diseases The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1 9 and 03 mu g/cm(2) per hour, respectively The bioavailability (BA) of alendronate in rats was approximately 8 3% after the application of alendronate patch and approximately 1 7% after oral administration These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases The plasma calcium level was effectively reduced after application of the alendronate patch in 1 alpha-hydroxyvitamin D-3-induced hypercalcemia model rats The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis Modest alendronate-induced erythema of rat skin was observed after application of the alendronate patch Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate-induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate These findings indicate that our novel transdermal

• 出版日期2010-12