Near -infrared spectroscopic monitoring of fluidized bed granulation: Process control and control of granule strength

William Paul Findlay, Purdue University

Abstract

The objectives of this research were to develop a model to use in combination with monitoring moisture content and particle size simultaneously in a fluidized bed granulator to determine the extent and mechanism of granule attrition during drying. By knowing a pre-determined granulation end-point (expected particle size and moisture content of the final granular product), the near-infrared (NIR) spectroscopic monitoring method was used in a real-time application to precisely determine when the granulation process had finished. The real-time measurements, combined with the mass and heat transfer behavior of the fluidized bed, provided a more robust method for determining the appropriate time points for the termination of binder addition, and the end of the drying cycle. The particle size enlargement during granulation wetting was fitted to a coalescence model. The drying curves measured real-time followed the established heat and mass transfer models. The use of these models makes altering a process to obtain a desired result during development a matter of science as opposed to trial and error (or relying only on experience). It was shown that a granulation dried at a lower fluidizing air temperature maintained a greater average particle size during drying than a granulation dried at a higher temperature. The amount of attrition due to both fracture and abrasion was lower in granulations dried at lower temperatures. The ability of a granulation to withstand attrition during fluidized bed drying did not correlate with the temperature of the material relative to the Tg of the polymer binder at the end of the granulation. The point at which the Tg passes the bed temperature, however, does correlate to an apparent change in attrition mechanism as well as to the end of the mass transfer limited drying stage. Additionally, granulations prepared with selected binder contents had varying attrition rates during fluid bed drying at the same drying temperature. The particle size change during drying was fit to the attrition models, and each granulation showed a different propensity for attrition. The real-time observed attrition correlated with the off-line attrition tests, indicating that a trend between attrition in the fluid bed and on the sieve exists.

Degree

Ph.D.

Advisors

Morris, Purdue University.

Subject Area

Pharmacology

COinS