Scale-down of a high-shear pelletisation process: Flow profile and growth kinetics

• Published in: International journal of pharmaceutics Vol. 166; no. 1; pp. 89 - 97
• Main Authors: Ramaker, J.S., Jelgersma, M.Albada, Vonk, P., Kossen, N.W.F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 11.05.1998; Elsevier
• Subjects: Biological and medical sciences; Flow; General pharmacology; Growth; Kinetics; Medical sciences; Pelletisation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Scale-down; Scale-down; Kinetics; Growth; Pelletisation; Flow; Particle size; Lactose; Shear; Pharmaceutical technology; Cellulose; Dosage form; Pellet(dosage form)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00030-1

For the predictive modelling of the high-shear pelletisation process it is necessary to have a better understanding of the underlying mechanisms. Therefore, pelletisation experiments were carried out with microcrystalline cellulose and lactose in a coffee grinder (small-scale) and in a Gral 10 (‘large’-scale). A toroidal flow-pattern was observed and described for both apparatus. There was no effect of increased impeller speed on the velocity of pellets in the torus; only a change in angle with the tangential direction was observed. Moreover, the size of pellets decreased rapidly to a new value. This size increased again when the impeller speed was reduced to the initial (low) value. This suggested the existence of fast break-up and growth, resulting in a dynamic equilibrium depending on the impeller speed. Tracer experiments were used to investigate the turnover times of different sieve fractions. First order conversion rate constants for the pellets of different sieve fractions, calculated from colour concentrations at several processing times, were equal for both apparatus when plotted against the dimensionless diameter of the pellets ( d/ d 50). These results are a strong indication for the usefulness of small-scale experiments to retrieve a rapid insight into relevant mechanisms of growth of high-shear pelletisation.