Nucleation regime map for liquid bound granules

Nucleation is the first step in granulation where the powder and liquid first contact. Two types of nucleation in wet granulation processes are proposed. Drop controlled nucleation, where one drop forms one nucleus, occurs when drops hitting the powder surface do not overlap (low spray flux Ψa) and the drop must wet quickly into the bed (short drop penetration time tp). If either criterion is not met, powder mixing characteristics will dominate (mechanical dispersion regime). Granulation experiments were performed with lactose powder, water, PEG200, and 7% HPC solution in a 6 L and a 25 L mixer granulator. Size distributions were measured as the drop penetration time and spray flux were varied. At short penetration times, decreasing Ψa caused the nuclei distribution to become narrower. When drop penetration time was high, the nuclei size distribution was broad independent of changes in dimensionless spray flux. Nucleation regime maps were plotted for each set of experiments in each mixer as a function of the dimensionless distribution width δ. The nucleation regime map demonstrates the interaction between drop penetration time and spray flux in nucleation. The narrowest distribution consistently occurred at low spray flux and low penetration time, proving the existence of the drop controlled regime. The nucleation regime map provides a rational basis for design and scale-up of nucleation and wetting in wet granulation.