Spheronisation
Encyclopedia
Spheronisation is a trademark of Caleva Process Solutions Ltd. and is the process where pellets are produced from mixtures of solids and liquids by the involvement of forming and shaping forces. Pellets range in size from about 0.5 to 2.0 mm. During this process, extrudates are shaped into rounded or spherical granules. This process was first reported by Reynolds and by Conine and Hadley in 1970.
In addition to this the process is useful in several aspects to improve the product; it can simplify plant procedures and help to reduce costs. The process is well known and widely used in the pharmaceutical industries but its use is becoming increasing recognized in other areas of industrial materials handling.
The latest advance is the development of a laboratory "Variable Density Extruder".
Spheronisers for development with the possibility to change bowl sizes are the preferred option so that the user can respond adequately to the requirements for the development of different batch sizes.
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 3 to 8 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.
Although the examination of the rheology of the product seems complex and potentially time consuming, and indeed can be so. With a Caleva Mixer Torque Rheometer (MTR-3) the ideal formulation can be determined very quickly and easily.
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.
Why consider spheronisation?
- The EMEA (The European Medicines Agency) regulation CPMP/QWP/604/96 states:-
- "The development of single unit non-disintegrating dosage forms is discouraged since their residence time in the stomach is unpredictable and in general longer than disintegrating dosage forms with multiple units of pellets. There, such single unit non-disintegrating dosage forms are liable to a higher risk of dose dumping."'
In addition to this the process is useful in several aspects to improve the product; it can simplify plant procedures and help to reduce costs. The process is well known and widely used in the pharmaceutical industries but its use is becoming increasing recognized in other areas of industrial materials handling.
Advantages of spheronisation relevant to pharmaceutical industries
spheronisation has many advantages. Not all of them will be relevant to all users. The main uses relevant to pharmaceutical product production and performance are:-- Easy to coat
- Separation of incompatible drugs
- Ability to mix pellets with different release rates
- Reduced risk of dose dumping
- Reduced risk of local irritation in the gastro-intestinal tract
- Less variable bio-availability
- Particles of 1mm or less behave more like liquids in terms of gastric emptying
- Even distribution over the gastro-intestinal tract.
Other Advantages of spheronisation relevant to other industries -
- The easy formulation and mixing of otherwise incompatible formulations.
- These have low surface to volume ratio that enables uniform film coating.
- Improved flow characteristics.
- Packing of beds and columns - In certain processes, porous beds or columns are used as chemical reactors. Spherical particles allow the reproduction of beds with *always the same void volume, surface area and permeability.
- To offer dust free packaging.
- To eliminate dust within the agro-chemical, pigment, and catalyst industries. This can reduce risk due to toxic, environmental, and explosive hazards.
- Density increase - Both the true and the bulk density of granules are increased by spheronising. This can improve the process and the packaging.
- Hardness and friability - Spheronisation increases the hardness and reduces the friability of granules. This will reduce the amount of fines generated during handling or transportation.
- Marketing - For consumer products, spheronising is sometimes only applied for improved product appearance and marketing
Mixing
The ingredients are generally mixed (or granulated - the process is called granulation) in either a high-shear granulator or a more simple planetary mixer.Extrusion.
The extrusion of the materials is a required step prior to spheronisation. The size of the spheres is principally determined by the diameter of the extrudate used for the spheronisation process. For example in order to obtain spheres with a diameter of 1 mm, a 1 mm screen is used on the extruder, although spheres with a slighter bigger diameter will sometimes be obtained. In a spheroniser, it is possible to obtain spheres with a diameter ranging from about 0.5 mm to about 10 mm but in practical terms the range is about 0.7 to 2 mm is considered normalThe latest advance is the development of a laboratory "Variable Density Extruder".
Spheronisation
Extrudate is charged to the spheroniser and falls on the spinning plate. During the first contact of the cylindrical granules with the friction plate, the extrudate is cut into segments with a length ranging from 1 to 1.2 times the 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 “rope movement” of product along the bowl wall. The continuous collision of the particles with the wall and with the friction plate will gradually turn the cylindrical segments into spheres, provided that the granules are plastic enough to allow the deformation without being destroyed or sticking together. It is essential that this rope movement is present for an optimal spheronisation. When the particles have reached the desired shape then the spheroids can be removed.Spheronisers for development with the possibility to change bowl sizes are the preferred option so that the user can respond adequately to the requirements for the development of different batch sizes.
Drying
Pellets need to be dried and this is generally done in a fluid bed drier. The fluid bed drier can also be used to coat the pellets.Machine Parameters
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. One principle specialist focusing on this technology is Caleva Process Solutions (www.caleva.com).Friction plate pattern.
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.
Friction plate speed.
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.
Retention time.
Typical spheronisation retention times to obtain spheres range from 3 to 8 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 charge volume
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.
Product parameters
The result obtained in the spheroniser depends on the rheology of the product (Rheology can be easily investigated using a Caleva Mixer Torque Rheometer - MTR-3). The particles must have enough plasticity to allow deformation under the impact they receive during the 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.- The rheologyRheologyRheology is the study of the flow of matter, primarily in the liquid state, but also as 'soft solids' or solids under conditions in which they respond with plastic flow rather than deforming elastically in response to an applied force....
of the product can be changed by using binders, lubricants, by changing the mixing time and by altering the liquid content of the mix. - Binders can be used to increase the strength of the granules and reduce the amount of fines generated during the spheronisation. If too much binder is added and the granules can become too hard, it will be difficult to obtain good spheres.
- Lubricants will increase the plasticity but may also increase the amount of fines generated during spheronisation.
- Water can also be used as a lubricant. If too much water is used, sticking can occur on the friction plate and bowl wall. It can also happen that the granules will stick together, forming big lumps. If the extrudate are too dry, a high amount of fines will be generated.
- The optimum moisture content for spheronisation is slightly less than for extrusion only.
Although the examination of the rheology of the product seems complex and potentially time consuming, and indeed can be so. With a Caleva Mixer Torque Rheometer (MTR-3) the ideal formulation can be determined very quickly and easily.
Auxiliary Equipment
There is various auxiliary equipment that can help to improve the efficiency and ease of the spheronisation process.
Water jacket.
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).
Air introduction (Fines air).
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.
Non-Stick Coatings
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.