Preparation of 200 mg fenofibrate hard capsule with high dissolution profile with microparticle entrapped micelles technology

Abstract

Fenofibrate, a drug of  fibrate class, is mainly used to reduce cholesterol levels in patients at risk of cardiovascular disease. However, bioavailability of fenofibrate is often low and unpredictably due to its poor solubility. Microparticle entrapped micelles (MEM) technology is a novel method of incorporating surfactants in solid dosage form for improving in vitro and in vivo performance of poorly water soluble drugs. Increasing the fenofibrate solubility by MEM technology has not been reported in the literature. In this study, the formulation of fenofibrate modified by MEM technology (FB-MEM) was studied. The FB-MEM was then  filled in the hard capsules with high dissolution profile. Fenofibrate was solubilized in various surfactants (tween 80, tween 60, Kolliphor P407, Acrysol K140, Gelucire 44/14) at different concentration of 0.5; 1; 3 and 5 % at cloud point temperature; the dispersion was dried to obtain solid product. The FE-MEM with highest solubility was then characterized by DSC and FTIR spectra. By using Acrysol K140 as surfactant, the FE- MEM solubility was enhanced up to 644 mg fenofibrate / 1 g surfactant. DSC diagram and FTIR spectra showed that there was no chemical interaction between fenofibrate and Acrysol K140. The high solubility of FE-MEM was thus possibly due to low melting point of this mixture and small size of FE-MEM. By using Primellose as disintegration excipient, hard capsule containing 200 mg of feno brate (FE-MEM) showed an equivalent dissolution profile with Lipanthyl (the similariry factor f2 = 53).