(178b) An Investigation into the Effects of Binder Viscosity, Shear Rate, Mixing Time, and Primary Particle Size on the Spreading of a Liquid in a Particle Bed
AIChE Annual Meeting
2008
2008 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Scale-up Issues in Pharmaceutical Formulation Development
Monday, November 17, 2008 - 3:35pm to 3:55pm
The purpose of the current study was to investigate the spreading of a liquid binder onto a particle bed while eliminating the effects of other phenomena that occur in a granulation process, namely agglomeration, breakage, and drying. It was desired to characterize this liquid spreading in terms of common parameters including liquid viscosity, shear rate in the powder bed, mixing time, and primary particle size. Furthermore, it was necessary to ensure as uniform a shear/velocity profile as possible in the particle bed so that all particles experience a similar environment in all regions of the bed. The experimental apparatus comprised of a tilted aluminum disk 2 feet in diameter driven by a motor, the speed of which could be manipulated by the user from a control panel. A plexiglass enclosure was constructed and was held in place on top of the rotating disk by springs. This enclosure acted as the walls of the particle bed. The shear in the particle bed was achieved by rotation of the disk that transferred momentum to the layer of particles in contact with the wall. The velocity profile of particles was S-shaped as measured through the side walls of the container. A series of experiments was performed to determine the effects of the aforementioned parameters on the uniformity of the coating on sugar cores (nonpareils). Silicone oils of viscosities ranging from 5 cSt to 10,000 cSt were used as the binder liquids. These silicone oils were blended with an isoparaffin to allow for the solubilizing of a blue dye in the silicone composition for visual marking purposes. Two shear rates were used for all coating runs. Three mixing times were investigated, namely 20 s, 60 s, and 200 s. Once the liquid spreading experiments were completed, the data were collected and analyzed. The coating uniformity was investigated by capturing images of the blue-coated particles with a color camera and subsequently analyzing the color level intensity on each particle using Visilog® imaging software. The relative standard deviation (RSD) of the blue content on the particle samples was determined from the raw data, and this RSD was used as a measure of the liquid spreading onto the particle bed. A high value indicates poor mixing while a low value indicates good/uniform mixing. It was found that liquid viscosity, shear rate, mixing time, and primary particle size all have an effect on the spreading of the liquid in the particle bed. The RSD was used as the dependent variable in the model and it was found to be a function of viscosity, maximum shear rate in the powder bed, mixing time, and primary particle size.
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