Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

Kwang-Ho Cha,^1,3 Kyung-Jin Cho,³ Min-Soo Kim,⁴ Jeong-Soo Kim,³ Hee Jun Park,^1,3 Junsung Park,^1,3 Wonkyung Cho,^1,3 Jeong-Sook Park,³ Sung-Joo Hwang<sup>1,2

1</sup>Yonsei Institute of Pharmaceutical Sciences, ²College of Pharmacy, Yonsei University, Incheon, Republic of Korea; ³College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; ⁴Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea

Background: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO₂.
Methods: Fenofibrate was loaded onto Neusilin^® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO₂. For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated.
Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO₂ facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO₂ were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate.
Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO₂ for improving the bioavailability of fenofibrate.

Keywords: fenofibrate, melt adsorption, supercritical CO₂, bioavailability

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