title: In vivo bioequivalence and in vitro similarity factor (f2) for dissolution profile comparisons of extended release formulations: how and when do they match?
abstract: OBJECTIVE
  To investigate how likely two extended release formulations are to be bioequivalent when they demonstrate f2 similarity.
  
  
  METHODS
  Dissolution profiles were simulated using the Weibull model and varying model parameters around those of a reference profile. The f2 values were calculated for the comparisons of each simulation with the reference profile. The in vivo inputs obtained from an in vitro-in vivo correlation model were convolved with a unit impulse response function. The AUC, Cmax, and Tmax from each simulated in vivo concentration profile were compared to the reference profile. The AUCR (AUC ratio) and CmaxR (Cmax ratio) were determined. The consistency between f2 and bioequivalence was investigated.
  
  
  RESULTS
  The relationships between AUCR, CmaxR, f2 and the Weibull model parameters demonstrate that the bioequivalence regions enclosed by the contour lines of 80% and 125% of AUCR and CmaxR were generally close to the regions enclosed by the f2 = 50 contour line, but did not exactly match, especially when Dmax and B deviated from the reference values.
  
  
  CONCLUSIONS
  When f2 is used for in vitro dissolution profile comparison, the completeness of the dissolution profiles should not differ more than 10%, and the shapes of the dissolution profiles should not be significantly different.
authors.affiliation: Office of New Drug Quality Assessment, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 21, Room 1620, Silver Spring, Maryland 20993, USA. John.Duan@fda.hhs.gov
authors.forename: John Z
authors.initials: JZ
authors.lastname: Duan
authors.forename: Kareen
authors.initials: K
authors.lastname: Riviere
authors.forename: Patrick
authors.initials: P
authors.lastname: Marroum
mesh_terms: D000818:Animals; D019540:Area Under Curve; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations