title: Is it possible to achieve bio-equivalence between an oral solid immediate-release and an analogue enteric-coated formulation?
abstract: OBJECTIVE
  While bioequivalence between enteric-coated and immediate-release formulations can be achieved in terms of AUC, gastric emptying of enteric-coated dosage forms is a stochastic event, usually leading to lower Cmax values than those observed with the corresponding immediate release. This article examines challenges of developing enteric-coated dosage forms which are bioequivalent to the corresponding immediate-release formulations in terms of both AUC and Cmax using rasagiline as a model compound.
  
  
  METHODS
  In vitro drug release profiles of enteric-coated formulations were obtained and compared to those of the immediate-release formulation by dissolution testing. Pharmacokinetics was evaluated in bioequivalence studies in healthy human volunteers after single oral administration of enteric-coated and immediate-release formulations.
  
  
  RESULTS
  The initial enteric-coated pellet formulation prototype was equivalent in terms of AUC, but differed in Cmax ; a second formulation prototype, consisting of a single-unit core and enteric-coating film, proved to be bioequivalent to immediate-release rasagiline tablets in terms of AUC and Cmax . In vitro, it released rasagiline rapidly at a pH of 6.8.
  
  
  CONCLUSIONS
  Despite differences in gastric emptying between disintegrating immediate-release and enteric-coated solid dosage forms, bioequivalence in pharmacokinetic studies was achieved.
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel.
authors.forename: Dannit
authors.initials: D
authors.lastname: Licht
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Spiegelstein
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel.
authors.forename: Laura
authors.initials: L
authors.lastname: Rabinovich-Guilatt
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Zholkovsky
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gilbert
authors.affiliation: Department of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
authors.affiliation: Discovery and Product Development, Global Research and Development, Teva Pharmaceutical Industries, Ltd, Netanya, Israel. Muhammad.Safadi@teva.co.il.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Safadi
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D013608:Tablets, Enteric-Coated / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D013608:Tablets, Enteric-Coated
keywords: bioequivalence; delayed release; enteric coating; immediate-release