Micronization of a poorly water-soluble drug, fenofibrate, via supercritical-fluid-assisted spray-drying

Purpose: In the present study, fenofibrate (a model drug with poor aqueous solubility) was micronized using the supercritical-fluid-assisted spray-drying (SA-SD) process to improve dissolution and biopharmaceutical property. Methods: Solid-state characterizations including particle size analysis and dissolution test were carried out. To identify the main effects of SA-SD process parameters (such as pressure, temperature, concentration of drug solution, supercritical carbon dioxide (SC-CO₂) injection rate, and drug solution injection rate) on the morphology and particle size distribution of micronized fenofibrate particles, a 2⁷⁻³_IV fractional factorial screening design was employed. Moreover, the effect of improved dissolution rate via micronization using SA-SD technology on the biopharmaceutical properties of fenofibrate was evaluated in a pharmacokinetic (PK) study in Sprague–Dawley rats. Results: The results of the screening design showed that the mean particle size and distribution can be controlled by manipulating the drug solution concentration and CO₂ injection rate. The SA-SD process resulted in a significant decrease in mean particle size (1.8–8.33 μm), as compared with that of unprocessed fenofibrate (24.2 ± 0.8 μm). There was a significant enhancement in the dissolution rate of micronized fenofibrate particles smaller than 5 μm compared to that of unprocessed fenofibrate. Moreover, an in vivo PK study in Sprague–Dawley rats showed that the increased dissolution rate improved biopharmaceutical properties (larger area under the curve and maximum serum concentration) of micronized fenofibrate than those of unprocessed fenofibrate. Conclusion: Therefore, the SA-SD process is a useful micronization technology for improving both physicochemical and biopharmaceutical properties of poorly water-soluble drugs.