title: Theoretical Investigation of Dissolution Test Criteria for Waiver of Clinical Bioequivalence Study.
abstract: The purpose of the present study was to provide a theoretical basis for the dissolution test criteria of a biowaiver scheme. The critical dissolution number (Dncrit) was defined as a value to show bioequivalence of AUC and Cmax against infinitely rapid dissolution (Dn = ∞). The gastrointestinal tract was represented by the one-compartment model. The dissolution of a drug was expressed by the Noyes-Whitney equation. The permeation of a drug was expressed by the first-order equation. The approximate analytical solutions of Dncrit were derived from the analytical solution for the fraction of a dose absorbed [Fa = 1 - exp(-1/(1/Dn + Do/Pn)]; Do, the dose number; Pn, the permeation number). Numerical integration was also performed to calculate Dncrit more accurately. Dncrit was found to become smaller as Pn and Do became smaller. Dncrit for Cmax was found to be dependent on the elimination half-life of a drug as well as Pn and Do. The Fa equation can be an appropriate theoretical basis for a biowaiver scheme.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan. Electronic address: kiyohiko.sugano@phar.toho-u.ac.jp.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Sugano
mesh_terms: D001702:Biopharmaceutics / Q000379:methods*; D003198:Computer Simulation; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012995:Solubility; D013810:Therapeutic Equivalency
chemical_list: D004364:Pharmaceutical Preparations
keywords: bioequivalence; biopharmaceutics classification system; dissolution rate; elimination; formulation; mathematical model; oral absorption; permeability; simulations; solubility