Microemulsion formulation for enhanced absorption of poorly soluble drugs. II. In vivo study.
Oral administration study of microemulsion formulations, which are known to improve the bioavailability of poorly soluble drugs, was performed using rats. Nitrendipine was used as a poorly soluble model drug, and its absorption was enhanced significantly by employing the microemulsion formulations compared to a suspension or an oil solution. The effect of the fed state on the oral absorption of nitrendipine became insignificant with the microemulsion formulations, although it affected the absorption from the suspension formulation significantly. The absorption behavior also varied with the type of surfactant. The absorption from Tween 80-based formulation was very rapid, while HCO-60-based formulation showed prolonged plasma concentration profile. However, the absorption from BL-9EX (polyoxyethylene alkyl ether)-based formulation was hardly observed. Damage to the gastrointestinal mucosa, which seems to be a serious problem of surfactant-based formulations, also differed with the type of surfactant employed. HCO-60 and Tween 80-based formulations were mild to the organs, while BL-9EX-based formulation caused serious damage. The behavior and absorption mechanism of the microemulsion formulations are discussed.
Kawakami
Kohsaku
K
Developmental Research Laboratories, Shionogi & Co., Ltd., 12-4 Sagisu 5-chome, Fukushima-ku, 553-0002, Osaka, Japan. kohsaku.kawakami@shionogi.co.jp
Yoshikawa
Takayoshi
T
Hayashi
Takashi
T
Nishihara
Yoshitaka
Y
Masuda
Kazuyoshi
K
D000284:Administration, Oral; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D004655:Emulsions / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009568:Nitrendipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D002121:Calcium Channel Blockers; D004655:Emulsions; D009568:Nitrendipine