Biowaiver Studies of Atenolol Tablets (100mg) - An Alternative to In Vivo Bioequivalence Studies
The aim of present study was to compare the quality of atenolol tablets and examine the possibility of biowaiver study for approval of generic drugs without additional in vivo bioequivalence study. Atenolol, a cardio selective β-blocker, could be clearly classified into BCS Class III and may be evaluated under biowaiver conditions. Due to the importance of atenolol and availability of different generics in a community basis, four products available in Ras Al Khaimah were analyzed. Four brands of atenolol 100 mg tablets have been evaluated using some quality control parameters, such as weight variation, hardness, content assay, disintegration and dissolution test. In vitro dissolution testing can be used in some cases not only to determine the quality of the pharmaceutical products but also to demonstrate bioequivalence to the generic product. Similarity factor (f2) and Difference Factor (f1) were used to assess bioequivalency among four products. The FDA recommended dissolution medium for atenolol is 0.1N HCl but it shows a good releasing pattern in water also. The dissolution profiles of Aten-4 and Aten-2 in pH 1.2 is rapid and good, only Aten -3 failed to cross the similarity factor but f1 is within limit. In pH 4.5 and 6.8 all brands fulfilled biowaiver requirements, except Aten-2 in pH 6.8 that may be due to manufacturing process difference. In the same time Aten-2 has f1 value 12 that is within the limit. Therefore, generic drugs with differing in vitro dissolution will not necessarily exhibit different in vivo performance. The results suggest that the formulation and/or the manufacturing process affect the dissolution and thus the bioavailability of the drug products. Thus the significance of the observed in-vitro differences must be confirmed by an in-vivo bioequivalence study.