The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70？mg, alendronate 70？mg plus vitamin D 5600？IU, and risedronate 35？mg) and generic (Novo-alendronate 70？mg and Apo-alendronate 70？mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly faster for Apo-alendronate ( seconds) and Novo-alendronate ( seconds) as compared to brand alendronate ( seconds), brand alendronate plus vitamin D ( seconds), or brand risedronate ( seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies. 1. Introduction Three-year randomized, controlled phase III clinical trials have established that the brand amino-bisphosphonates alendronate [1, 2], risedronate [3, 4], and zoledronic acid [5, 6] are generally safe and provide significant antifracture efficacy at vertebral, nonvertebral, and hip sites. Consequently, the amino-bisphosphonates are considered first-line therapy for the treatment of individuals at high risk for fracture [7]. In phase III clinical trials, therapies are assessed for two primary outcomes: efficacy and safety. Phase III trials for brand antifracture medications require large samples (>5000 patients), due to the relative low rate of fragility fracture, and a lengthy duration of observation (at least three years), in order to demonstrate efficacy and long-term safety. Contrastingly, approval for the production, marketing, and sale of generic versions of brand bisphosphonates do not require similar investigations [8]. In Canada, generic versions of a brand drug are adjudicated for approval by Health Canada, which takes into consideration the active ingredient, product strength, disease indication, route of administration, quality, and bioequivalence in comparison to the innovator product [9]. Bioequivalence of generic and brand products is assumed when dissolution and short-term bioavailability studies are completed for the generic and are found to be within an acceptable range as compared with the innovator product (90% confidence interval of the ratio of the mean area under the curve and peak concentration
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