In vitro and in vivo evaluation of sustained release chitosan-coated ketoprofen microparticles.
Simple ketoprofen microspheres (MS) were prepared by the dry-in-oil method using ethylcellulose (EC) as a matrix polymer. Further, the microspheres modified by addition of polyethylene glycol (PEG) and hydroxypropyl cellulose (HPC), called MS-P and MS-H, respectively, were prepared. The in vitro release from MS, MS-P and MS-H was examined in the JP XIII second fluid, pH 6.8, at 37 degrees C and 60 rpm. Chitosan-coated ketoprofen microparticles (Chi-MP) were prepared by the precipitation of droplets of chitosan solution containing MS, and their adhesion to the rat small intestinal mucosa was tested. The plasma concentrations after duodenal administration were investigated for ketoprofen powder suspension, MS and Chi-MP. The particle size was raised with the increase in amount of ketoprofen added. The drug content and addition of PEG or HPC affected the drug release rate. The microspheres with moderate drug content, prepared by addition of modest amount of PEG, exhibited better gradual drug release. Chi-MP showed a good mucoadhesion. The maximum plasma concentration of ketoprofen for Chi-MP was less than one-third of that for ketoprofen powder suspension. Chi-MP tended to show the higher and steadier plasma level than MS.
Department of Drug Delivery Research, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
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Yamada
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Onishi
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Machida
D000327:Adsorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D003692:Delayed-Action Preparations; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007660:Ketoprofen / Q000493:pharmacokinetics; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D013256:Steroids; D002686:Chitin; D011092:Polyethylene Glycols; D002482:Cellulose; D048271:Chitosan; D007660:Ketoprofen; C008079:hydroxypropylcellulose