Material Process: Extrusion-Spheronization
Extrusion-Spheronization is the traditional method for manufacturing pellets. Agglomeration through the extrusion and spheronization process has been used for many years. In fact, this process dates back to 1950’s when the first pelletized dosages were introduced to the market. These pelletized dosages gain popularity quickly due to their noticeable advantages. For example, it is easier to fill the capsule, enhance the drug dissolution, coat the pill, and control the delivery of ingested drug. These pills can be formed through a wide variety of techniques such as spray drying, spray congealing, hot-melt extrusion, and spheronization of low melting materials 9.
The figure above shows the classification of pelletization techniques. The extrusion-spheronization process is listed under compactation. Agitation is when the finely divided particles are transformed into spherical particles by balling. The appropriate quantity of liquid is added to the finely divided particles during a continuous rolling motion. Compactation is a form of pressure agglomeration where the particles are forced together or compressed in order to form pellets of the desired shape and size. The particles rearrange themselves to form a closely packed mass during compression. This means that during higher pressure, the particles are forces against each other. However, they are so tightly packed already. As a result, the particles are elongated and undergo elastic and plastic deformation. In the extrusion-spheronization process, the dry powder is first agglomerated with the aid of a binding liquid. Next, it is processed in the extruder to produce high density extrudates (material that has been extruded through a die). These extrudates are finally converted to pellets on spheronizer.
Layering is the deposition of successful layers of drug particles from solution, suspension, or dry powder on the nuclei. There are 3 types of layering: powder, solution, and suspension layering. Out of the three, the suspension layering has been proven to be superior to the other two in terms of drug loading and enteric layering phase. Globulation is process where hot melt, solution, or suspension are atomized to generate spherical pellets. In the spray drying process, the atomized globules, or droplets, come in contact with a hot gas. This is when the droplets start to evaporate. Temperature, humidity, and transport properties of the air surrounding the droplet are all adjustable variables to form the ideal pellet. In the spray congealing, the temperature of the atomized droplets are lowered to below the melting point of the vehicles such as gums, wax, fatty acids, etc. A critical requirement in this process is that substances should have well-defined melting points or small melting zones.
The extrusion-spheronization technique is the most traditional and one of the most popular method for producing pellets. This process involves four steps: granulation, extrusion, spheronization, and lastly, drying of the pellets. Granulation is the process of forming into grains or granules and is involved with the preparation of plastic mass. Different types of granulators are used to perform the mixing of the powder blend and the granulation liquid. The 3 most commonly used granulators are planetary mixer, high-shear, and sigma blade mixer. The prepared plastic mass undergoes extrusion at which the pressure is applied to a mass until it flows out through an orifice to produce the extrudates. The extrudate length may vary on a few factors. These factors include the physical characteristics of the materials to be extruded, method of extrusion, and how particles are manipulated after extrusion. In spheronization, the extruded, cylindrically shaped particles are broken into uniform lengths. They will eventually have a spherical shape due to elastic and plastic deformation. Once the extrudates are broken into nearly uniform lengths andall three dimensions of agglomerate shape are determined, spherical pellets with a nearly uniform diameter are produced. The figure below shows the fundamental components of the spheronizer. The most important component is the friction plate. The last step of the process is the drying of the pellets. The pellets can be either dried at room temperature or at elevated temperature in a fluidized bed or in an oven 10.
Some parameters that govern the extrusion-spheronization process are the velocity, temperature, spheronizer load, and spheronizer time. The extrusion velocity is important because it governs the total output of the extrudate. The output will always be as high as possible since that would increase profit. However, an increase in the velocity can affect the quality of the pellet. The spheronizer velocity also affects the quality of the pellet. If the spheronizer velocity is too low, there will be no significant changes in the extrudate. However, if the velocity is too high, there will be a size reduction of the particles. In addition, hardness, roundness, porosity, bulk and tapped densities, friability, flow rate and surface structure of the pellets are dependent on the spheronizer velocity. The extrusion temperature is important because it determines if the water that was used for the preparation of spherical granules will evaporate. The final form of the pill should not contained any liquid or water; it should have been evaporated. As a result, the pellet can be stored for a longer period of time. The spheronizer load affects the yield amount of pellets. By increasing the spheronization velocity and using a low spheronizer load, the yield decreased. However, by extending the spheronization time and using a higher spheronizer load, the yield increased. In addition, mean diameter increases with an increasing spheronizer load. The last parameter is spheronizer time which has a significant influence on the quality of the pellets. With an extended spheronizer time, a narrower particle size distribution and a higher sphericity can be achieved. Thus, the most spherical pellets are achieved by using a large number of holes during extrusion, a high spheronizer speed and longer time of spheronization 11.
It can be concluded from the above equation that due to the logarithmic relationship, a slight increase in filler solubility can result in a large increase in the extrusion force for very soluble fillers. However, for insoluble fillers, there is such a small difference that it is negligible.
The above equation shows that an increase in the filler and the drug solubility will result in a reduction in the pellet fraction size.
The above equation proves a significant linear relationship between the pellet density and the filler and drug level. If the filler or drug level increases, then there is an increase in pellet density. However, the pellet density will decrease if there is a decrease in filler solubility. This is common due to the high density of the insoluble fillers.
The above equation describes the relation between porosity and the drug level and filler solubility. An increase in the drug level will lead to an increase in porosity. However, an increase in filler solubility will result in a decrease in porosity. This means that soluble materials will decrease the porosity in pellets. .
The above equation shows that an increase in the drug level will lead to a decrease in the strength of the pellets 12.
The extrusion-spheronization process transfers heat via convection. When the pellet is spheronizing, the wet granules must be dried through the evaporation of the liquid. The wet granules come in contact with the hot gas and over time, the shape of a spherical pellet is formed. In addition, all liquid have been evaporated at this point. This process is convective because it uses the hot gas as a material medium in order to transfer the heat into the wet granule. In addition, this process is a forced convection because one is introducing an external source of heat in the form of hot gas. Furthermore, there is no buoyancy force due to the density gradient.