High Shear Granulation/Fluid Bed Drying/Dry Milling
A typical high shear granulation process involves mixing the active ingredient and possibly some excipients in a mixer. The binder may be one of the excipients added in the dry mix state or dissolved in the fluid used for granulating. The granulating solution or suspension is added to the dry powders in the mixer and mixed until the desired characteristics are achieved. This usually produces a granule that will be of suitable characteristics for producing tablets with adequate hardness, dissolution, content uniformity, and other physical characteristics. After the wet granulation step, the product is most often dried and then milled after drying to get a major percentage of the product within a desired size range. Sometimes, the product is dried after being wet sized using a device such as an oscillating granulator, or a mill such as a Granumill® or a cone mill. The dry granulation is then processed to get an acceptable size range by first screening with a sieving device, and then milling the oversized particles. The granulation particle size distribution is not extremely narrow and usually contains a significant percentage of undesirable fines and coarse particles. For normal compressed tablets, the broad particle size range produced by this method is usually satisfactory. For other specialty applications, a different technique is desired.
A possible variation of the above wet milling approach for producing a very fine uniform granulation is to wet mill the granulation to a very small particle size and then dry it. In actual practice, when a granulation has been made wet enough to accomplish the desired characteristics such as dried hardness, it is too wet to be processed through a mill with a small enough opening size.
Top Spray Fluid Bed Granulation
A typical fluid bed granulation process involves fluidizing the active ingredients and possible some excipients in an air stream. The binder may be one of the excipients or dissolved in the fluid used for granulating. The granulating solution or suspension is sprayed onto the top of the fluidized bed using a spray nozzle until the desired characteristics are achieved. This very often results in a granulation that has a very low amount of fines. However, this process typically produces softer granules that do not hold up well during subsequent processing steps.
Extrusion and Spheronization
A typical extrusion and spheronization process starts with the active ingredients and excipients being granulated in a high shear mixer. The wet granulated material is discharged into an extruder which further densifies the product and discharges it as small pellets through a screen. The pellets are then transferred into a spheronizer which is a chamber with a rotating plate in the bottom. The pellets are spun around for a short period of time which turns the pellets into spheres. The spheres are then dried. This process produces a very spherical, durable granule. However, due to mechanical limitations on the extruder, it cannot effectively produce particles less than 35 mesh. In addition, the process throughput is limited by the spheronization step which typically can only handle very small amounts of product at a time.
Fluid Bed Rotor Granulation
A typical fluid bed rotor granulation process involves a special fluid bed chamber that has a spinning plate in the bottom. There is a gap between the spinning plate and the side wall of the chamber in which the air flows upward. As the plate spins and the air flows upward, powders are added to the chamber using a powder feeder, and liquid is sprayed in using a spray nozzle. This process can produce particles in different size ranges that are spherical and durable. However, the process takes a long time and has shown to be difficult to scale up.
