A study of in situ fluid bed melt granulation using response surface methodology.

The objective of this work was to investigate the influence of selected individual variables (binder content, inlet air temperature, and product endpoint temperature) of in situ fluid bed melt granulation on the granule particle size distribution and percentage of dissolved carvedilol using a three-factor, five-level circumscribed central composite design. Increased binder content had the effect of increasing the granule particle size and drug dissolution rate. The effect of inlet air temperature and product endpoint temperature was found to be more pronounced in case of granule particle size parameters. Within the studied intervals, the optimal quantity of binder as well as optimal process parameters were identified and validated using response surface methodology. Utilizing these optimal process and formulation parameters, successful scaling up of the fluid bed melt granulation process was carried out. Granule characteristics obtained at pilot scale are comparable to those obtained at laboratory scale.