European Journal of Biomedical and Pharmaceutical Sciences

UNEXPECTED DIFFERENCES IN DISSOLUTION BEHAVIOR OF TABLETS PREPARED FROM FENOFIBRATE SOLID DISPERSIONS AND STRONGLY ENHANCED DISSOLUTION RATE, EXCLUSIVELY BETTER THAN MARKETED PRODUCTS

Md. Zakaria Faruki*, Mohiuddin Ahmed Bhuiyan, Md. Fakrul Alam, Rishikesh, Rehana Akhter,
A K M Mofasser Hossain

ABSTRACT

Fenofibrate is used to reduce cholesterol levels in patients at risk of cardiovascular disease. As it is poorly water soluble drug, solid dispersions were prepared by different methods in our previous studies and were then formulated into 600 mg tablet equivalent to 40 mg of Fenofibrate. Different polymers like poloxamer 188, PVP, poloxamer 407, HPMC 6cps, PEG 6000 and mannitol were used to prepare the solid dispersions. Characterization of pre-compression (angle of repose, bulk density, tapped density, compressibility index, hausner ratio) and compression (thickness, hardness, weight variation, friability, drug content and disintegration tests) properties of the granules, powder and tablets were evaluated. In this study, it was shown that the incorporation of super disintegrant, sodium starch glycolate (SSG), in solid dispersion tablets containing a high drug load can strongly enhance the dissolution rate of the highly lipophilic drug fenofibrate. In addition, the dissolution rate was increased when SSG was incorporated in the tablet containing solid dispersions than when it was physically mixed with the solid dispersions. Solid dispersion tablets based on poloxamer 188 (99.37%), PVP (92.68%), poloxamer 407 (92.58%) showed a much faster dissolution than those based on HPMC 6 cps (85.23%), PEG 6000 (79.20%) and mannitol (72.32%). But Tablet which prepared only physical mixing with excipients without any technique released only 26.31%. The differences in dissolution behavior of tablets prepared from solid dispersions were very much unexpected. The dissolution rate enhancement strongly depended on super disintegrants and type of hydrophilic polymers used in the formulations. Maximum formulations displayed highest fitting with Higuchi release pattern and some formulations also displayed with Korsmeyer release model for solid dispersion. Lowest number fitted with zero order kinetic model of drug release. The dissolution profiles of formulated tablets were compared with the marketed products which showed exclusively better release profile than marketed products.

Keywords: Fenofibrate, solid dispersion technique, dissolution, tablet, marketed products.