Advances in Process Controls and End-Point Determination

Abstract

GRANULATION: THE ESSENTIAL PROCESS Process control in one way or another is as old as granulation technology itself. It can be imagined that during pill-rolling, a druggist would evaluate the consistency of the dough for ease in rollability. If pills of insufficient quality were prepared, additional binders or solvents would be added accordingly. Bringing this art of preparing elegant medicaments into industrial pharmacy would have been a natural progression. It is further imagined that this marks the origin of the notable end-point detection method of the squeeze test. This test would be performed during wet massing to assess the quality and indirect binder saturation of the granulation. Through trial and error, the formulator would determine the optimal binder and binder quantity. After gaining more experience with the operation, soon the experienced operator was able to hear when a wet granulation process was nearing completion. This was due to the increased load on themixing equipment secondary to the adhesive wet mass. In the case of drying granulations in a fluid-bed dryer, one might feel the expansion chamber for increasing temperature to determine the end point of drying. These historical methods take considerable time to “develop” and are reliant solely on empiricism and intuition. Nonbiased techniques to determine process end point have been sought. This necessary transition was to ensure that reproducible products are manufacturing in a reliable way. It is suggested that arising out of being able to “hear” the granulation end point because of the increased load on the mixer are power consumption and torque measurements. More recently, passive acoustic technology has been found to be a successful methodology for determining granulation end point (1).