Evaluation Of Quality Consistency Of Bisoprolol Fumarate Tablets

Objective:To establish a method for determination of dissolution of bisoprolol fumarate tablets;evaluate the consistency of imported generic preparations,domestic generic preparations and original preparations;evaluate the consistency of different batches of original preparations,imported generic preparations and domestic generic preparations;evaluate the consistency of split tablets and complete tablets of the 5 mg specification and evaluate the consistency of half tablets of 5 mg specification and complete tablets of the 2.5 mg specification.Methods:The dissolution rates of original preparations,imported generic preparations and domestic generic preparations were determined in water,pH 1.2 hydrochloric acid solution,pH 4.0 acetate buffer solution and pH 6.8 phosphate buffer solution,by stirring paddle method(rotating rate75 r·min^-1)and the established HPLC method?stationary phase C18,detection wavelength 225 nm?respectively,and the similarity of dissolution profiles was evaluated by the similarity factor?f₂?method.Results:1.The established HPLC method had a good specificity and the concentration had a good linearity relationship with the peak area in the range of 0.5-16 mg·L^-1;The RSD?n=9?of intermediate precision was lower than 2%,and recovery rates were in the range of 90-108%?n=3?.Neither slight changes of rotating rate nor temperature contributed to significant effect on the dissolution behavior of the drug?P>0.05?.2.In the 4 kinds of dissolution medium,f₂ of the dissolution profiles of imported generic preparations and original preparations A was more than or equal to 50,f₂ of domestic generic preparations A and original preparations A was only partially more than or equal to 50,f₂ of domestic generic preparations C and original preparations A was less than 50,f₂ of domestic generic preparations B and original preparations B was only partially more than or equal to 50,and f₂ of domestic generic preparations D and original preparations B was less than 50.3.In the 4 kinds of dissolution medium,f₂ of the dissolution profiles of three batches of original preparations A,B,imported generic preparations and domestic generic preparations A,B,D was respectively more than or equal to 50;f₂ of the dissolution profiles of three batches of domestic generic preparations C was only partially more than or equal to50.4.In the 4 kinds of dissolution medium,f₂ of the dissolution profiles of split tablets and complete tablets of original preparations A and imported generic preparations was respectively more than or equal to 50,f₂ of the dissolution profiles of split tablets and complete tablets of generic preparations A,C was only partially more than or equal to 50,f₂ of the dissolution profiles of half tablets of 5 mg specification and complete tablets of the 2.5 mg specification of Merck KgaA?original preparations?was only partially more than or equal to 50,f₂ of the dissolution profiles of half tablets of 5 mg specification complete tablets of the 2.5 mg specification of manufacturer 1?domestic generic preparations?or manufacturer 2?domestic generic preparations?was respectively more than or equal to 50.Conclusion:1.The established HPLC method is suitable for the dissolution determination of bisoprolol fumarate tablets and the dissolution method is robust.2.The dissolution behavior between imported generic preparations and original preparations A is consistent;the dissolution behavior between domestic generic preparations A,C and the original preparations A is inconsistent;and the dissolution behavior between domestic generic preparations B,D and the original preparations B is inconsistent.3.The dissolution behavior between three batches of original preparations A,B,imported generic preparations and domestic generic drug A,B,D is consistent;and the dissolution behavior between three batches of domestic generic preparations C is inconsistent.4.The dissolution behavior is consistent between split tablets and complete tablets of original preparations A,but inconsistent between half tablets of it and complete tablets of 2.5 mg specification of the same manufacturer of it;the dissolution behavior between split tablets and complete tablets of imported generic preparations A was consistent;and the dissolution behavior was inconsistent between split tablets and complete tablets of domestic generic preparations A or C respectively,but consistent between half tablets of them and complete tablets of 2.5 mg specification of the same manufacturers of them.