Application of the correlation of in vitro dissolution behavior and in vivo plasma concentration profile (IVIVC) for soft-gel capsules--a pointless pursuit?
Plasma concentration profiles of arundic acid ((R)-(-)-2-propyloctanoic acid), an oil-like medicine, administered as soft-gel capsules in human clinical tests were predicted from the dissolution test data of the soft-gel capsules with different storage terms (short- and long-term stored drugs) by applying the in vitro-in vivo correlation (IVIVC). We established two linear-regression IVIVCs, which were characterized by either the in vitro dissolution behaviors against the pH 8.0 dissolution medium or the pH 6.8 dissolution medium containing 2% sodium dodecyl sulfate (SDS), in this study. Also, the prediction accuracies for the in vivo plasma profiles in humans for these two IVIVCs were compared. Regarding dissolution from the long-term stored capsule in pH 8.0 dissolution medium without surfactant, the prediction accuracies of the in vivo plasma profiles in humans were not satisfactory for the obtained IVIVC. The use of pH 6.8 dissolution medium containing 2% SDS, according to the Japanese guideline, improved the dissolution of the long-term stored capsule. Furthermore, the prediction accuracies for the in vivo plasma profiles in humans for these two IVIVCs were compared. The IVIVC established by the in vitro dissolution data obtained with the dissolution medium containing surfactant more effectively predicted the plasma drug concentration profiles following oral administrations of the soft-gel capsules under both storage conditions.
Nishimura
Hidekatsu
H
Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama, Japan.
Hayashi
Chiaki
C
Aiba
Tetsuya
T
Okamoto
Ichiro
I
Miyamoto
Yuji
Y
Nakade
Susumu
S
Takeda
Kazuhisa
K
Kurosaki
Yuji
Y
D000284:Administration, Oral; D002021:Buffers; D002210:Caprylates / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002214:Capsules; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D004355:Drug Stability; D005782:Gels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology; D016014:Linear Models; D008954:Models, Biological; D011237:Predictive Value of Tests; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
D002021:Buffers; D002210:Caprylates; D002214:Capsules; D005782:Gels; C459360:ONO2506; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate