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

• Published in: International journal of pharmaceutics 2021-01, Vol.593, p.120101-120101, Article 120101
• Main Authors: Mamidi, Hemanth K., Palekar, Siddhant, Nukala, Pavan Kumar, Mishra, Saurabh M., Patki, Manali, Fu, Yige, Supner, Piyush, Chauhan, Gautam, Patel, Ketan
• Format: Article
• Language: English
• Subjects: Co-processed excipient; Design of Experiments (DoE); Fenofibrate; Melt granulation; Twin-screw granulator
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.120101

[Display omitted] 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 × 3 factorial design was used to optimize the processing conditions using the % drug loading (X1) and screw speed (X2) as the independent parameters and granule friability (Y1) % yield (Y2) 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 (X1) and % friability (Y1) and a quadratic relationship was observed between the independent parameters (X1 and X2) and % yield (Y2). 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® as the super disintegrating agent. The optimized formulation showed >85% drug release in 0.75% SLS solution within 60 min.