Dansereau Richard J, Crail Debbie J, Perkins Alan C
Procter & Gamble Pharmaceuticals, Inc., Mason, OH 45040-9462, USA.
Curr Med Res Opin. 2008 Apr;24(4):1137-45. doi: 10.1185/030079908x280725. Epub 2008 Mar 10.
The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax).
The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison.
The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification.
The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not adequate to establish similar disintegration characteristics.
本研究旨在评估加拿大、德国、荷兰和英国市场上26种70毫克阿仑膦酸钠片剂的体外崩解和溶出情况，并与品牌产品（福善美）进行比较。
采用美国药典30（USP 30）中所述方法测定崩解和溶出时间。纳入四种口腔崩解片（非双膦酸盐类）和品牌薄膜包衣利塞膦酸钠片的崩解情况进行比较。
阿仑膦酸钠片剂的平均崩解时间从荷兰Pharmachemie公司产品的14秒到德国Betapharm公司产品的342秒（5.7分钟）不等。品牌产品片剂的平均崩解时间在43至78秒之间。26家公司中有6家销售崩解时间极快的阿仑膦酸钠片剂，其与口腔崩解片（非双膦酸盐类）相似。崩解时间极快的阿仑膦酸钠片剂如下：荷兰Pharmachemie公司产品，14秒；加拿大Novopharm公司产品，13 - 24秒；德国GRY-Pharma公司产品，21秒；德国Juta Pharma公司产品，30秒；英国APS/Teva公司产品，26秒和37秒；以及英国Teva公司产品，14 - 29秒。由于阿仑膦酸钠片剂没有既定的崩解时间，因此无法保证仿制药片在食管药物暴露方面与品牌产品等效。然而，体外崩解时间与体内崩解及性能并无关联。所有双膦酸盐片剂的溶出均迅速，15分钟内溶出超过80%，且所有产品均符合USP 30标准。
所有阿仑膦酸钠片剂的溶出迅速且完全，符合既定的USP 30标准，这应能确保仿制药有足够的药物吸收。然而，阿仑膦酸钠片剂仿制药是基于健康受试者单剂量生物利用度研究结果获批的，这不足以确立相似的崩解特性。
