No abstract

The in-line FBRM and SFT probes were successfully employed in in situ fluid bed melt granulation process to study the influence of critical formulation/process parameters on the granule growth kinetics. The scale-up experiment confirmed the potential of these in-line granule size measurement techniques as a viable tool for process monitoring during the transfer of granulation to the larger scale or another manufacturing site/equipment.

Melt granulation belongs to the group of hot-melt technologies, which represent an alternative to the classical solvent-mediated technological processes of agglomeration. The main advantage of hot-melt processes, including melt granulation, is the absence of solvents, which can be efficiently utilized in enhancing chemical stability of moisture sensitive drugs and also improving their physical properties. Moreover, a drying phase is eliminated, which results in a more economical and environmentally friendly process. There are also some limitations in using melt granulation processes. The major drawback is the required high temperature during the process, which can cause degradation and/or oxidative instability of the ingredients, especially of thermolabile drugs (1, 2).Equipment used for melt granulation technologies must be modified to promote melting and prevent unwanted solidification of the product on exposed equipment sur- 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.