Nicotinamide pelletization by fluidized hot melt granulation: L18 Hunter design to screen high risk variables.

L18 Hunter design was used to investigate the practicability of applying QbD approaches to fluidized hot melt granulation (FHMG) in preparing oral controlled release systems. Eight high-risk variables obtained from risk analysis were classified into chemical factors (type and percentage of meltable binder, matrix viscosity and percentage and filler type) and process variables (size fraction of meltable binder, inlet air volume and fluidization time). The variables were screened for their impacts on pellets characteristics. The obtained results showed that the meltable binder percentage was the significant variable affecting most responses. Flow properties, size distribution, bulk, and tapped densities were significantly (P<0.05) affected by the filler type, inlet air volume, and fluidization time. On the other hand, the matrix variables were non-significant to the dissolution parameters. Out of eight critical variables, it was found that the meltable binder percentage and size fraction, inlet air volume had the most significant effects and will be optimized in the second part of the study. In conclusion, QbD paradigm not only offered a robust FHMG technique to formulate controlled release formulations of hydrophilic drugs but also provided a time and cost saving advantage to pharmaceutical industry.