In the production of pharmaceutical pellets, the process of Extrusion & Spheronization (ES) is commonly used. This four step process consists of wet mixing, extrusion, spheronization, and drying/coating. The pellets are then encapsulated, tabeleted, or dosed into sachets. Pharmaceutical pellets range in size from 0.6 to 1.2 mm.
Spheronization, also known as Marumerization (Japanese origin), is the third step in the ES process. During this step, cylindrical extrudates (from the previous step) are converted into spheres (see detailed description below).
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The process is well known and widely used in the pharmaceutical industries but its use is becoming increasing recognized in other industries.
The ingredients are generally mixed (or granulated - the process is called granulation) in either a high-shear granulator or a more simple planetary mixer.
The wet mass (or granulation) is extruded on low pressure extruders (such as Dome, Radial, or basket extruders) to form cylindrical extrudates of a constant diameter (0.6 - 1.2 mm). The wet mass is wiped through the screen forming soft, pliable extrudates (similar to pasta) which break by their own weight into shorter unit. The size of the final pellets (spheres) is principally determined by the hole diameter of the screen (or die) used in the extrusion step. For example in order to obtain spheres with a diameter of 1mm, a 1mm screen is used on the extruder, although spheres with a distribution of 0.8-1.2 mm may sometimes be obtained.
Spheronization is a batch process. Extrudates are charged to the spheronizer and falls on the spinning plate. During the first contact of the cylindrical granules with the friction plate, the extrudates are cut into segments with a length ranging from 1 to 1.2 times their diameter. These segments then collide with the bowl wall and they are thrown back to the inside of the friction plate. Centrifugal force sends the material to the outside of the disc. The action of the material being moved causes the extrudate to be broken down into pieces of approximately equal length related to the diameter of the extrudate. These cylindrical segments are gradually rounded by the collisions with the bowl wall and the plate and each other. The ongoing action of particles colliding with the wall and being thrown back to the inside of the plate creates a “twisting rope movement” of product along the bowl wall. The continuous collision of the particles with the wall and with the friction plate gradually converts the cylindrical segments into spheres, provided that the extrudates are plastic (pliable) enough to allow the deformation without being destroyed or sticking together. It is essential that this rope movement is present for an optimal spheronization. When the particles have reached the desired level of sphericity, they are then discharged from the spheronizer.
Wet pellets are collected and dried in a vertical fluid bed drier (FBD). The FBD can also be used to coat the pellets (using a Wurster insert) if so desired.
In principle the basic machine consists of a round disc with rotating drive shaft, spinning at high speed at the bottom of a cylindrical bowl. The spinning friction plate has a carefully designed groove pattern to the base. This is most often cross-hatched, several sizes and other types available. These discs are designed to increase the friction with the product. Spheronisation equipment is available from several manufacturers.
The most common groove pattern used for spheroniser discs is the “waffle-iron” or cross-hatch design, where the friction plate is like a chessboard of chopped-off pyramids. The choice of which disc type and size to use is rather empirical. Discs with a radial design are also used, as these are considered gentler on the material being spheronised.
The typical rotation speed of a 700 mm diameter disc ranges from 400 to 500 rpm. The higher the speed, the more energy is put into the particle during a collision. The optimum speed depends on the characteristics of the product being used and the particle size. In general, smaller discs require a high speed while bigger discs require lower speeds. In practice the optimum speed can be determined from experience and systematic testing. For some products it might be recommendable to start at a high speed and to lower the speed in the final stage of the process. But again this can be determined by simple practical tests. The process allows a high degree of flexibility for most materials.
Typical spheronisation retention times to obtain spheres range from 2 to 6 minutes. As with speed this is relatively easy to determine and best obtained by simple trials with specific products. For some products, the strong cohesive forces in the extrudate prevent the extrudate from breaking up into smaller pieces. If the objective is to reduce dust and not necessarily obtain perfect spheres than the short contact with the friction plate is sufficient to break the long extrudate into small segments and round the edges. The edges of cylindrical granules are the most fragile part and they will generate dust during handling and transportation. Spheronisation with a short retention time can help to reduce this amount of dust significantly.
The optimum level depends upon the machine size and the product characteristics; there is an optimum quantity of product to be charged per batch into the spheroniser chamber that will produce the most narrow particle distribution and the best spheres. Increasing the load per batch increases the hardness of the spheres and smooths the granule surface.
The result obtained in the spheroniser depends on the rheology of the product. The particles must have enough plasticity to allow deformation under the impact they receive during the spheronization process, but also must be strong enough to withstand the collisions with the friction plate, each other and bowl wall without being broken up and destroyed.
There is various auxiliary equipment that can help to improve the efficiency and ease of the spheronisation process.
Warm or cooling water can be introduced in a jacket. Warm water can be particularly useful on the chamber wall to drive off moisture that would cause product sticking on that wall. Cooling the wall will avoid temperature rises in heat sensitive products, although, the average temperature rise in a spheroniser is generally rather small (normally about 4°C).
A slight flow of air can be introduced in the chamber from under the friction plate this not only prevents dust from getting between the rotating plate and the wall of the chamber but also can help to remove moisture from the granule’s surface, improving the friction forces and the process efficiency.
For some products, the chamber wall and the spheronisation plate can be coated with non-stick materials if this is necessary for ease of use with sticky materials or cleaning.