title: The mean dissolution time depends on the dose/solubility ratio.
abstract: OBJECTIVE
  To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model.
  
  
  METHODS
  Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a dimensionless quantity by taking into account the volume of the dissolution medium. Our results were applied to in vitro and in vivo data taken from literature.
  
  
  RESULTS
  We found that MDT depends on q when q < 1 and is infinite when q > 1 and that the classic expression of MDT = 1/k. where k is the dissolution rate constant, holds only in the special case of q = 1. For the case of perfect sink conditions, MDT was found to be proportional to dose. Using dissolution data from literature with q < 1, we found better estimates of MDT when dependency on dose/ solubility ratio was considered than with the classic approach. Prediction of dissolution limited absorption was achieved for some of the in vivo drug examples examined.
  
  
  CONCLUSIONS
  The mean dissolution time of a drug depends on dose/ solubility ratio, even when the model considered is the simplest possible. This fact plays an important role in drug absorption when absorption is dissolution limited.
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, University of Athens, Athens 15771, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Rinaki
authors.forename: Aristides
authors.initials: A
authors.lastname: Dokoumetzidis
authors.forename: Panos
authors.initials: P
authors.lastname: Macheras
mesh_terms: D000465:Algorithms; D004305:Dose-Response Relationship, Drug; D008790:Metoprolol / Q000493:pharmacokinetics; D008954:Models, Biological; D010599:Pharmacokinetics; D012995:Solubility; D013607:Tablets
chemical_list: D013607:Tablets; D008790:Metoprolol