Particle design using fluidized hot melt granulation

Fluidized hot melt granulation (FHMG) is an emerging technique combining the advantages of both dry and wet granulation methods, and represents an innovative continuous granulation process capable of mixing and agglomerating excipients and active pharmaceutical ingredients (APIs) to produce uniform blends of particles suitable for use in the manufacture of pharmaceutically elegant solid dosage forms. This study investigates the influence of process parameters and formulation variables on the FHMG of two model pharmaceutical systems using either polyethylene glycol (PEG) or a copolymer of polyoxyethylene/ polyoxypropylene (Lutrol F68, BASF; Ludwigshafen, Germany). Granule growth within the FHMG process reached equilibration after a defined period for both model systems. The Lutrol F68 system reached equilibration after 2.5 min, whereas PEG required at least 5 min. The equilibration time significantly decreased as the molecular weight (Mw) of PEG increased from 6000 to 10000. Granule growth for these systems proceeded via a coalescence mechanism, which decreased significantly as the molecular weight of the binder increased. Increasing the binder content within the systems increased the mean particle diameter until a threshold value was reached (20% w/w PEG and 10% w/w Lutrol F68), after which the system defluidized and an overwetted mass was produced. Interestingly, the regularity of the granules was shown to be dependent upon the binder concentration within the fluidized system. Increased binder content resulted in irregular granules, whereas lower binder contents produced highly spherical granules.