title: Effect of Seed Particles on Precipitation of Weak Base Drugs in Physiological Intestinal Conditions.
abstract: The purpose of the present study was to investigate the effect of seed particles on the precipitation behavior of weak base drugs in the small intestine. A simple in vitro infusion method was used to mimic in vivo processes. Dipyridamole, pioglitazone, topiroxostat, chlorpromazine, cinnarizine, and ketoconazole were used as model drugs. A drug was dissolved in 0.01 N HCl and infused into a pH 6.5 buffer. The existence of seed particles significantly affected the concentration-time profiles of the model drugs in the buffer. The maximum concentration was significantly reduced in the presence of seed particles (except for cinnarizine). In the case of dipyridamole, pioglitazone, and topiroxostat, the precipitants were crystalline from the beginning of precipitation. In contrast, the precipitants of ketoconazole, cinnarizine, and chlorpromazine were a mixture of amorphous and crystals. In conclusion, the presence of seed particles significantly affected the precipitation behavior of weak base drugs.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University , 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University , 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University , 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University , 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Sugano
mesh_terms: D000818:Animals; D002746:Chlorpromazine / Q000737:chemistry; D002936:Cinnarizine / Q000737:chemistry; D004176:Dipyridamole / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D007654:Ketoconazole / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D000077205:Pioglitazone; D011725:Pyridines / Q000737:chemistry; D012995:Solubility; D045162:Thiazolidinediones / Q000737:chemistry
chemical_list: D009570:Nitriles; D011725:Pyridines; D045162:Thiazolidinediones; C504882:FYX-051; D002936:Cinnarizine; D004176:Dipyridamole; D007654:Ketoconazole; D002746:Chlorpromazine; D000077205:Pioglitazone
keywords: amorphous; crystal; gastric pH; oral absorption; precipitation; seed particle; weak base