Enhancement of the dissolution rate and gastrointestinal absorption of pranlukast as a model poorly water-soluble drug by grinding with gelatin.
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.
Chono
Sumio
S
Department of Pharmaceutics, Hokkaido Pharmaceutical University, 7-1 Katsuraoka-cho, Otaru-city 047-0264, Japan. s-chono@hokuyakudai.ac.jp
Takeda
Eri
E
Seki
Toshinobu
T
Morimoto
Kazuhiro
K
D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D002867:Chromones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D017097:Electric Impedance; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
D018927:Anti-Asthmatic Agents; D002867:Chromones; D011208:Powders; D005780:Gelatin; C047681:pranlukast