Dissolution study and thermal analysis of fenofibrate–Pluronic F127 solid dispersions

Bożena Karolewicz,Janusz Pluta,Agata Górniak,Maciej Gajda

doi:10.1007/s10973-015-5013-2

Bożena Karolewicz, Janusz Pluta + Show 2 more

Open Access

https://doi.org/10.1007/s10973-015-5013-2

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Abstract

Prepared solid dispersions were applied to a drug with low water solubility to improve its dissolution rate. Fenofibrate (FEN) is a Biopharmaceutical Classification System (BCS) class-II (poorly water-soluble) drug, and its bioavailability is limited by the dissolution rate. The physical state of FEN in solid dispersions with Pluronic F127 (PLU) prepared using the fusion method was assessed using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). The DSC investigation revealed that FEN and PLU form a simple eutectic system. The DSC, XRPD, and FTIR studies of the investigated solid dispersions revealed no interaction between FEN and PLU. The intrinsic dissolution rate (IDR) of FEN from solid dispersions was significantly increased compared with the pure drug. The enhancement in the intrinsic dissolution rate was approximately 134-fold for solid dispersions containing 30/70 % w/w of FEN/PLU.

Highlights

Fenofibrate (FEN) (isopropyl ester of 2-[4-(4-chloro-benzoyl) phenoxy]-2-methylpropanoic acid) is a Biopharmaceutical Classification System (BCS) class-II, lowsolubility, high-permeability hypolipidemic drug [1]
The differential scanning calorimetry (DSC) curves of the mixtures indicate that FEN and Pluronic F127 (PLU) formed a simple binary eutectic system—only two kinds of thermal effects are shown for the entire range of compositions
The onset of the first peak consistently appeared near 45.3 °C (Fig. 2), which indicated the following eutectic reaction: Solid fenofibrate ðFENÞ þ solid Pluronic F127 ðPLUÞ 1⁄4 liquid ðLÞ: The second peak, which corresponds to the temperature of liquid, was generally wider

Summary

Introduction

Fenofibrate (FEN) (isopropyl ester of 2-[4-(4-chloro-benzoyl) phenoxy]-2-methylpropanoic acid) is a Biopharmaceutical Classification System (BCS) class-II, lowsolubility, high-permeability hypolipidemic drug [1]. The FEN solid dispersions in EudragitÒ E100 and polyvinylpyrrolidone–vinyl acetate copolymer S630 (PVP– VA) were prepared using a hot-melt extrusion method, which improved the dissolution and the bioavailability of the drug [4]. The solid dispersion of FEN in Poloxamer 188 and tocopheryl polyethylene glycol succinate as a surfactant prepared using spray drying significantly increased the dissolution rate of this drug [7]. Improvements in the FEN dissolution property were observed for solid dispersions of the drug with Poloxamer 407 and Poloxamer 407 microprepared using a physical mixing technique [19]. The DSC scans of each mixture were performed at a heating rate of 5 °C min-1 in the temperature range from 25 to 200 °C. 10/90 FEN/PLU 20/80 FEN/PLU 30/70 FEN/PLU 40/60 FEN/PLU 50/50 FEN/PLU 60/40 FEN/PLU 70/30 FEN/PLU 80/20 FEN/PLU 90/10 FEN/PLU

Results and discussion

Eutectic temperature

Conclusions