title: Biowaiver monographs for immediate release solid oral dosage forms: rifampicin.
abstract: Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing rifampicin as the only Active Pharmaceutical Ingredient (API) are reviewed. Rifampicin's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and absolute BA data indicate that rifampicin is a BCS Class II drug. Of special concern for biowaiving is that many reports of failure of IR solid oral dosage forms of rifampicin to meet BE have been published and the reasons for these failures are yet insufficiently understood. Moreover, no reports were identified in which in vitro dissolution was shown to be predictive of nonequivalence among products. Therefore, a biowaiver based approval of rifampicin containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.
authors.affiliation: Institute of Pharmaceutical Technology, J.W. Goethe University, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Becker
authors.forename: J B
authors.initials: JB
authors.lastname: Dressman
authors.forename: H E
authors.initials: HE
authors.lastname: Junginger
authors.forename: S
authors.initials: S
authors.lastname: Kopp
authors.forename: K K
authors.initials: KK
authors.lastname: Midha
authors.forename: V P
authors.initials: VP
authors.lastname: Shah
authors.forename: S
authors.initials: S
authors.lastname: Stavchansky
authors.forename: D M
authors.initials: DM
authors.lastname: Barends
mesh_terms: D000284:Administration, Oral; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D004304:Dosage Forms; D017277:Drug Approval; D004355:Drug Stability; D005079:Excipients; D018565:Food-Drug Interactions; D006801:Humans; D007917:Leprostatic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010539:Permeability; D012293:Rifampin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012995:Solubility; D013810:Therapeutic Equivalency
chemical_list: D000904:Antibiotics, Antitubercular; D004304:Dosage Forms; D005079:Excipients; D007917:Leprostatic Agents; D012293:Rifampin