Development of a new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract.
A new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract was developed. In this new system, a drug (solid form) is added into a drug-dissolving vessel (pH 1.0) and the dissolved drug is transferred to a pH adjustment vessel (pH 6.0). Then the drug solution is transferred to the apical surface of Caco-2 cells, and the permeation rate of the drug across a Caco-2 monolayer is determined. This system was able to predict the oral absorption ratios of ten water-soluble drugs in humans. Using this system, it was predicted that drugs that permeated Caco-2 at a rate of more than 0.1% of the dose in 200 min would be almost completely absorbed after oral administration in humans. For a drug whose permeation ratio was less than 0.03%, the absorption ratio was predicted to be less than 30%. This system also enabled prediction of the absorption rate and variability in the absorption of albendazole, a drug with poor water solubility. It also enabled assessment of the improvement in absorption using a solid dispersion of albendazole-polymers that improved the water solubility. The results suggest that this system is useful for oral absorption screening of new drugs and pharmaceutical products.
Kobayashi
M
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan.
Sada
N
N
Sugawara
M
M
Iseki
K
K
Miyazaki
K
K
D000284:Administration, Oral; D018938:Caco-2 Cells / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D010599:Pharmacokinetics; D011237:Predictive Value of Tests; D012995:Solubility