Three Levels Face Centered Central Composite Design of Colon Targeted Micro-Particulates System of Celecoxib: Screening of Formulations Variables and in vivo Studies
Bankim Chandra Nandy, Vinod Verma, Sanjay Dey and Bhaskar Mazumder
Affiliation: Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh-786004, Assam, India.
Keywords: Celecoxib, Central composite-face centered design, Colon targeted delivery system, In vivo x-ray studies, Response
Surface Methodology (RSM).
Celecoxib is a well known non-steroidal anti-inflammatory drug (NSAID) and extensively employed for the
treatment of arthritis. The aim of the present study was to design, develop and optimization of micro particulates system,
for colon specific delivery of celecoxib for both local (in prophylaxis of colorectal adreno-carcinoma) and systemic (in
chrono-therapeutic treatment of arthritis) 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 micro-particulates system of celecoxib. Microspheres
were formulated with the combination of ethyl cellulose (EC) and eudragit RS100/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 and XRD analysis. The formulation variables were optimized by response surface
methodology (RSM). Best optimized delayed release formulation was further subjected to the in vivo x-ray studies to
evaluate the site specificity. It was found that in-vitro release (Y1-Y3
) decreased significantly (p<0.05) with increase in
amount of eudragit polymer but increased significantly (p<0.05) with an increase in surfactant concentration and stirring
speed. FTIR study indicated that no strong chemical interaction took place between the drug and excipients of prepared
formulations. DSC and XRD studies indicated that drug was present in the amorphous state. The X-ray photographs revealed
that the swelling layer eroded from the outer surface and a size reduction was seen after 6 hrs when optimized microspheres
reached the site of colon. Therefore, this approach suggested that the combination of eudragit S100 and ethyl
cellulose microspheres may be useful for the delivery of maximum amount of celecoxib in intact form to the colon.
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