Formulation and characterizations of delayed release multi particulates system of indomethacin: optimization by response surface methodology.
Indomethacin is a widely used non-steroidal anti-inflammatory drug (NSAID) and extensively employed for treatment of arthritis. Delayed action (at the morning or night) is needed for arthritic patients. To improve the patient compliance, in this study we aimed to delay the drug release by designing multi-particulates system in the form of microspheres, which would efficiently release the drug into the colon and replace the conventional therapy. The aim of the present work was to elucidate the effect of formulation variables e.g., amount of eudragit polymer (X1), surfactant concentration (X2) and agitation speed (X3) on in-vitro release profiles (Y1-Y3), drug entrapment efficiency (Y4) and particle size (Y5) of multi-particulates system of indomethacin. Experiments were designed according to a three levels face centered central composite design. Microspheres were formulated with the combination of ethyl cellulose (EC) and Eudragit RS 100/Eudragit S100; by using a novel quasi emulsion solvent diffusion technique. Developed formulations were characterized and evaluated on the basis of FTIR, thermal, particle size, SEM, XRD analysis and drug release kinetics studies. The formulation variables were optimized by response surface methodology (RSM). It was found that in-vitro release (Y1-Y3) was decreased significantly (p<0.05) with increase in amount of eudragit polymer but increased significantly (p<0.05) with increase in surfactant concentration and stirring speed. It was observed that the drug release data of the selected formulation was similar to the predicted release pattern. FTIR study indicated that no prominent chemical interaction or changes took place between the drug and excipients of prepared formulations. DSC and XRD studies indicated that drug was present in the amorphous state and may have been homogenously dispersed into the polymers matrix. Therefore this approach suggested that the combination of EC and Eudragit S100 microspheres may be useful in a better way, for the delivery of maximum amount of indomethacin in intact form to the colon.
Bankim Chandra
BC
Nandy
Bhaskar
B
Mazumder
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008956:Models, Chemical; D015233:Models, Statistical; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D013501:Surface-Active Agents; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose; D007213:Indomethacin