Development of a novel transdermal patch of alendronate, a nitrogen‐containing bisphosphonate, for the treatment of osteoporosis

• Published in: Journal of bone and mineral research 2010-12, Vol.25 (12), p.2582-2591
• Main Authors: Kusamori, Kosuke, Katsumi, Hidemasa, Abe, Mari, Ueda, Asuka, Sakai, Ryota, Hayashi, Rie, Hirai, Yuka, Quan, Ying‐shu, Kamiyama, Fumio, Sakane, Toshiyasu, Yamamoto, Akira
• Format: Article
• Language: English
• Subjects: Alendronate - administration & dosage; Alendronate - blood; Alendronate - pharmacokinetics; Alendronate - therapeutic use; Animals; Biological and medical sciences; BISPHOSPHONATES; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - blood; Bone Density Conservation Agents - pharmacokinetics; Bone Density Conservation Agents - therapeutic use; Bones, joints and connective tissue. Antiinflammatory agents; Butylated Hydroxytoluene - pharmacology; Calcium - blood; Female; Growth Plate - drug effects; Growth Plate - pathology; Humans; Hypercalcemia - blood; Hypercalcemia - complications; Hypercalcemia - drug therapy; Hypercalcemia - prevention & control; Medical sciences; Nitrogen - therapeutic use; OSTEOPOROSIS; Osteoporosis - blood; Osteoporosis - complications; Osteoporosis - drug therapy; Ovariectomy; Permeability - drug effects; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Rats, Wistar; SKIN; Skin - drug effects; Skin - pathology; Skin Irritancy Tests; TRANSDERMAL DELIVERY; Transdermal Patch
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.147

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 0.3 µg/cm2 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 1α‐hydroxyvitamin D3–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 delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases. © 2010 American Society for Bone and Mineral Research.