Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound.
The usefulness of selected biorelevant dissolution media (BDM) to predict in vivo drug absorption was studied. Dissolution profiles of solid formulations of a poorly soluble model compound were compared in BDM simulating fasted and two levels of fed state. A non-physiologically relevant medium containing the cationic surfactant, cetrimide, was also investigated. All the media studied were capable of differentiating between the formulations employed, with formulation A consistently ranking high and formulations C and D ranking low. An in vivo dog study was carried out and an attempt was made to obtain a level A correlation between the plasma absorption curves and in vitro dissolution curves, using non-linear regression software. The in vitro-in vivo correlation (IVIVC) models developed indicated that fed state media (BDM 3) containing high levels of both bile salts (BS) and lipolysis products (LP) were best able to predict in vivo pharmacokinetic parameters (Cmax and AUC) with prediction errors lower than 10%. Overall, design and use of appropriate media for in vitro dissolution is extremely important. This study demonstrates the potential of physiologically relevant media containing both BS and LP for use in formulation and early drug development.
Lue
Bena-Marie
BM
Department of Pharmaceutics and Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark.
Nielsen
Flemming Seier
FS
Magnussen
Thomas
T
Schou
Hanne Mette
HM
Kristensen
Kim
K
Jacobsen
Lene Orup
LO
Müllertz
Anette
A
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004304:Dosage Forms; D005079:Excipients; D005260:Female; D007700:Kinetics; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility; D012997:Solvents
D000891:Anti-Infective Agents, Local; D002593:Cetrimonium Compounds; D004304:Dosage Forms; D005079:Excipients; D004364:Pharmaceutical Preparations; D012997:Solvents; D000077286:Cetrimonium