RRC ID 43076
Author Chono S, Takeda E, Seki T, Morimoto K.
Title Enhancement of the dissolution rate and gastrointestinal absorption of pranlukast as a model poorly water-soluble drug by grinding with gelatin.
Journal Int J Pharm
Abstract The effect of grinding with gelatin on the dissolution behavior and gastrointestinal absorption of a poorly water-soluble drug was evaluated using the antiasthmatic agent, pranlukast, as a model poorly water-soluble drug. A ground pranlukast-gelatin mixture was prepared by grinding equal quantities of pranlukast and gelatin. In the dissolution testing, the dissolution rate of pranlukast in the suspension of the ground pranlukast-gelatin mixture under conditions of pH 3.0, 5.0 and 7.0 was markedly faster than that in the suspension of pranlukast. According to powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) analysis, the enhanced dissolution rate of pranlukast produced by grinding with gelatin was caused by changing the crystalline state of pranlukast into an amorphous state. In an animal experiment, the bioavailability of pranlukast following oral administration of the ground pranlukast-gelatin mixture to rats was threefold greater than that following administration of pranlukast. In the in vitro permeation experiment, the amount of permeated pranlukast through Caco-2 cell monolayers after application of the ground pranlukast-gelatin mixture was greater than that after application of pranlukast. These results suggest that the enhancement of the gastrointestinal absorption of pranlukast by grinding with gelatin is due to enhancement of the dissolution rate. Grinding a poorly water-soluble drug with gelatin is a useful method of enhancing its gastrointestinal absorption.
Volume 347(1-2)
Pages 71-8
Published 2008-1-22
DOI 10.1016/j.ijpharm.2007.06.037
PII S0378-5173(07)00554-6
PMID 17689212
MeSH Administration, Oral Animals Anti-Asthmatic Agents / administration & dosage Anti-Asthmatic Agents / chemistry Anti-Asthmatic Agents / pharmacokinetics Area Under Curve Biological Availability Caco-2 Cells Calorimetry, Differential Scanning Chromones / administration & dosage Chromones / chemistry Chromones / pharmacokinetics* Drug Stability Electric Impedance Gelatin / chemistry* Humans Hydrogen-Ion Concentration Intestinal Absorption* Male Powders Rats Rats, Sprague-Dawley Solubility X-Ray Diffraction
IF 4.845
Times Cited 30
Human and Animal Cells CACO-2(RCB0988)