The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations.
The aim of this study was to compare the oral absorption of two weak bases including their pH-independent controlled-release preparations using an in vitro evaluation system. This system is able to simulate dissolution of drugs, pH change and permeation of drugs through the epithelial cell membrane in the gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent sustained-release granules of dipyridamole were prepared by using a solvent method. Elution profiles and predicted absorption of these preparations in gastric pH conditions similar to those in healthy subjects and patients with achlorhydria were compared with those of a physical mixture and commercial tablets. When a physical mixture or commercial tablets were used, the elution profile and predicted absorption of both albendazole and dipyridamole were extremely pH-dependent. On the other hand, when a solid dispersion and granules were used, elution and predicted absorption were not affected by changes in pH of the flowing solution in a drug-dissolving vessel. These results are in agreement with the results of our previous in vivo study using gastric acidity-controlled rabbits. Our results suggest that this in vitro system is useful for the evaluation of oral absorption of pH-independent controlled-release preparations.
Sugawara
Mitsuru
M
Department of Pharmacy, School of Medicine, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan.
Kadomura
Shota
S
He
Xin
X
Takekuma
Yoh
Y
Kohri
Naonori
N
Miyazaki
Katsumi
K
D000126:Achlorhydria / Q000378:metabolism; D000284:Administration, Oral; D015766:Albendazole / Q000737:chemistry / Q000378:metabolism; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism*; D003911:Dextrans; D015194:Diffusion Chambers, Culture / Q000295:instrumentation / Q000379:methods*; D004176:Dipyridamole / Q000737:chemistry / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005744:Gastric Acid / Q000737:chemistry; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D011108:Polymers; D012995:Solubility
D003692:Delayed-Action Preparations; D003911:Dextrans; D011108:Polymers; C015219:fluorescein isothiocyanate dextran; D004176:Dipyridamole; D015766:Albendazole; D016650:Fluorescein-5-isothiocyanate