Sustained release ketoprofen microparticles with ethylcellulose and carboxymethylethylcellulose.
Microparticulate systems for sustained release of ketoprofen were prepared and evaluated by monitoring drug release in the JP XIII second fluid, pH 6.8. All the microparticulate dosage forms were prepared using ketoprofen in the form of calcium salt (KP-Ca). Simple ethylcellulose microparticles of KP-Ca (EC-MP) exhibited the fairly rapid release in the first phase with slower release in the late period. Most of the drug was released from EC-MP showing high drug content. For polymer-coated microparticles of ketoprofen, Eudragit microparticles of KP-Ca (ER-MP) were first prepared, and then coated with ethylcellulose or with a mixture of carboxymethylethylcellulose and ethylcellulose to produce ethylcellulose-coated (EC-coat) and the mixture-coated microparticles (CMEC/EC-coat), respectively. Some polymer-coated microparticles showed drug release at nearly zero-order rate. Especially, CMEC/EC-coat prepared at a CMEC:EC ratio of 1:1 (w/w), named formation I, could supply the drug constantly and efficiently for about half a day except for an initial rapid release. When formation I was administered intraduodenally to rats, the plasma concentration of ketoprofen could be maintained at a nearly constant level. Kinetic analysis demonstrated that formation I showed a nearly zero-order release rate in vivo consistent with that observed in vitro.
Yamada
T
T
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan.
Onishi
H
H
Machida
Y
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002482:Cellulose / Q000008:administration & dosage* / Q000031:analogs & derivatives; D003692:Delayed-Action Preparations; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; C013517:ethyl cellulose; D002482:Cellulose; D007660:Ketoprofen