Process optimization of twin-screw melt granulation of fenofibrate using design of experiment (DoE)

The purpose of this study was to optimize the melt granulation process of fenofibrate using twin-screw granulator. Initial screening was performed to select the excipients required for melt granulation process. A 3 x 3 factorial design was used to optimize the processing conditions using the % drug loading (X-1) and screw speed (X-2) as the independent parameters and granule friability (Y-1) % yield (Y-2) as the dependent parameters. The effect of the independent parameters on the dependent parameters was determined using response surface plots and contour plots. A linear relationship was observed between % drug loading (X-1) and % friability (Y-1) and a quadratic relationship was observed between the independent parameters (X-1 and X-2) and % yield (Y-2). The processing conditions for optimum granules were determined using numerical and graphical optimization and it was found that 15% drug loading at 50 rpm results in maximum % yield of 82.38% and minimum friability of 7.88%. The solid-state characterization of the optimized granules showed that the drug turned from crystalline state to amorphous state during melt granulation process. The optimized granules were compressed into tablets using Purolite (R) as the super disintegrating agent. The optimized formulation showed >85% drug release in 0.75% SLS solution within 60 min.

Automated summary

This study aimed to optimize the melt granulation process of fenofibrate using twin-screw granulator. By utilizing a factorial design, the optimal processing conditions for high yield and low friability of granules were determined. The solid-state characterization of the optimized granules showed a transition of the drug from crystalline to amorphous state during the melt granulation process, leading to >85% drug release within 60 min in a 0.75% SLS solution.