title: Application of dissolution/permeation system for evaluation of formulation effect on oral absorption of poorly water-soluble drugs in drug development.
abstract: OBJECTIVE
  The aim of the present study is to evaluate the formulation effect on the oral absorption of poorly water-soluble drugs using a dissolution/permeation system (D/P system).
  
  
  METHODS
  This D/P system, consisting of apical and basal chambers and a Caco-2 cell monolayer mounted between chambers, can be used to perform simultaneous analysis of drug dissolution and permeation process of drugs applied as various dosage forms. Oral administration study with rats was also performed for both drugs as the same dosage forms.
  
  
  RESULTS
  When danazol, a low-soluble and high-permeable drug, was applied to the D/P system as various formulations, dissolved and permeated amounts were significantly high compared with those from a suspension form. On the other hand, whereas the dissolved amount of pranlukast, a low-soluble and low-permeable drug, was significantly increased by formulations, there were no significant changes observed in the permeated amount between suspension and formulation. The oral availability of danazol was significantly increased by formulations but not pranlukast, which corresponded well to in vitro evaluations.
  
  
  CONCLUSIONS
  These results indicated that the D/P system might be applicable for selection of formulation on the basis of physicochemical drug properties.
authors: Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan. makoto@pharm.setsunan.ac.jp
authors: Makoto
authors: M
authors: Kataoka
authors: Kiyohiko
authors: K
authors: Sugano
authors: Claudia
authors: C
authors: da Costa Mathews
authors: Jing Wen
authors: JW
authors: Wong
authors: Kelly Lane
authors: KL
authors: Jones
authors: Yoshie
authors: Y
authors: Masaoka
authors: Shinji
authors: S
authors: Sakuma
authors: Shinji
authors: S
authors: Yamashita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D002867:Chromones / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D003613:Danazol / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002867:Chromones; D003613:Danazol; C047681:pranlukast