Enhancement of dissolution of Fenofibrate by Solid dispersion Technique

Abstract

Fenofibrate is a lipid lowering drug used in the treatment of hyperlipidemia, which is not soluble in water and lower absorption in gastric fluid. In order to improve the solubility and oral absorption of the drug in gastric fluid and to enhance its dissolution rate solid dispersions and Lyophilization of dispersion is designed and evaluated. Solid dispersions of Fenofibrate were prepared using PEG 6000, Poloxamer 407 and a mixture of PEG 6000 and Poloxamer 407(1:1 mixture). The effect of melt and solvent methods of preparation of solid dispersion on dissolution behavior was also investigated. Dissolution studies indicated a significant increase in dissolution of Fenofibrate when dispersed in PEG6000 and Poloxamer 407. Physical mixtures containing PEG and Poloxamer 407 also showed improved dissolution of Fenofibrate as compared with that of pure drug, indicating the solubilizing effect of PEG6000 and Poloxamer 407. Solid dispersions containing Fenofibrate /Poloxamer 407, 1: 8, showed a 14-fold increase in dissolution after 60 min (D60) and another dispersion containing Fenofibrate /PEG 6000, 1:10, showed an 8-fold increase in the 0.1 N HCl systems. The dispersion containing six parts of the PEG 6000: Poloxamer 407 mixture (PEG 4000/PEG 6000, 1:1 mixture) showed a 12-fold increase in D60 as compared with pure drug. When multi-carrier solid dispersion containing six parts of mixture was prepared by the solvent method, the D60 value was about 2-fold that of the same dispersion prepared by the melt method. The dissolution of lyophilized solid dispersions further increased the dissolution of Fenofibrate significantly.