Formulation and Characterizations of Delayed Release Multi-Particulates System of Indomethacin: Optimization by Response Surface Methodology
Bankim Chandra Nandy and Bhaskar Mazumder
Affiliation: Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh-786004, Assam, India.
Keywords: Central composite-face centered design, Colon targeted delivery system, Delayed release, Indomethacin, Multiparticulates
system, Response surface methodology (RSM).
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.
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