High shear wet granulation machine 200kg

High shear wet granulation machine 200kg

High shear wet granulation

The two adjectives "high shear" and "wet process" in the name of this technology reveal its core process characteristics. Wet method refers to the addition of wetting agents such as water, ethanol, or their mixtures during the granulation process, which will be removed in subsequent processes. And high shear relies on a dedicated high shear wet granulation machine, whose high-speed rotation of the stirring blade and cutting blade generates strong shear force, causing wet particles to be dispersed into small particles, and through the rotation of the stirring blade, the small particles adhere to the dry material that has not been wetted, thus continuously growing, cutting, wetting, and ultimately forming particles of the desired size. The key features of this process include the wetting agent being pumped into droplets that are much larger in size than the base material particles, as well as the high shear force causing the initial wet particles to disperse.

The second type of granulation technology is spray granulation, which involves spraying adhesive (or wetting agent) into granulation materials after atomization. When the atomized adhesive comes into contact with the material particles, these particles will "stick" and adhere to other materials during the movement process, repeating this process until the desired size of particles is formed. The key feature of this granulation method is that the size of the atomized droplets of the wetting agent (or adhesive) (usually less than or equal to 150 μ m) is similar to or smaller than the size of the base material particles (about 100 μ m).

2. High shear wet granulation

In the process of high shear wet granulation, the principle of "shear granulation" is inevitably involved. By precisely controlling the liquid adding spray gun, the sprayed liquid can contain a certain proportion of "small droplets", so that the effect of "spray granulation" can be achieved while wet granulation. Usually, in the case of high shear wet granulation, the proportion of "shear granulation" will exceed 70%. However, by selecting appropriate spray nozzles and flow control, the proportion of "atomization granulation" can be significantly increased, making it possible to reach over 50%.

The principle of incorporating "atomization granulation" into high shear wet granulation is mainly based on the following considerations:

Firstly, 'shearing granulation' relies on strong 'high shear force'. However, in practical operation, we cannot guarantee that every particle will receive uniform shear. As the scale of granulation equipment expands, the degree of crushing of large particles will gradually decrease, resulting in a relatively wide distribution of particle size. In contrast, "atomization granulation" is easier to control, with the key being the "size of atomized droplets". This parameter not only facilitates uniform granulation within a single batch, but also maintains good reproducibility during equipment scaling up.

Secondly, the performance of the high shear granulator is crucial for the granulation effect. If the equipment performance is poor, the granulation effect will be greatly reduced, and even reproducibility may not be guaranteed. In the process of equipment scaling up production, sometimes the available high shear wet granulation machine may only be limited to the "active" level, and in this case, the "atomization granulation" factor may become the key to improving granulation efficiency.

In addition, standard high shear wet granulation does not include "atomization granulation". Generally, the better the equipment performance, the lower the dependence on "atomization granulation". But in some cases, in order to achieve good atomization effect and ensure granulation quality, it may be necessary to reduce the spraying speed, which may prolong the granulation time by up to 25 minutes.

From the perspective of granulation, these considerations have practical significance. Especially in the field of generic drugs, homemade formulations need to reproduce the granulation state of the reference formulation as much as possible. If the reference formulation does not use "atomization granulation", its particle size and softness range may be wide, which may make it difficult for homemade formulations to reproduce their dissolution characteristics through simple "atomization granulation". Therefore, in the development process of generic drugs, various factors need to be comprehensively considered to ensure consistency in granulation effect between homemade formulations and reference formulations.

The change in particle size is a crucial step in the production process of solid dosage forms. High shear wet granulation, as an important technology, can be divided into several key steps: firstly, the pre mixing stage, which usually lasts for 0 to 5 minutes; The next stage is the slurry addition phase, which is divided into two periods, namely 5 to 15 minutes and 15 to 20 minutes; Next is the granulation stage, which takes about 20 to 25 minutes; Finally, there is the process of discharging whole pellets, which is the wet grinding process. Next, we will delve into each of these stages in depth.

Pre mixing stage

This step aims to thoroughly mix the active ingredients with the excipients, achieved through the high-speed rotation of the stirring blade or the combination of the stirring blade and the cutting blade. The mixing time is usually set between 3 minutes and 15 minutes, with common options being 5 minutes or 10 minutes. The evaluation standard for mixed quality is to sample 10 points for testing, ensuring that the RSD (relative standard deviation) does not exceed 0%, and ideally should be below 0%. If the mixing effect is poor, the mixing time can be extended or the stirring speed can be increased. It should be noted that granulation is not involved in this stage, so the particle size remains unchanged.

Slurry Stage I

In this step, the adhesive (or wetting agent) is added to the wet granulator through a spray gun. If the spraying is uniform, this process takes about 1/2 to 3/4 of the overall spraying time. The stirring blade maintains normal speed, while the cutting blade can remain closed or in a low or high speed state. At this point, dust can be observed through the sight glass and filter bag, and there is a slight increase in particle size. When using a high-speed hydraulic spray gun, this process may only take 5 minutes; When using an atomizing spray gun, it may take 10 to 15 minutes.

Slurry Stage II

As the adhesive continues to be added, the material in the wet granulation machine gradually becomes wetted, the dust decreases, and the granulation particles rapidly increase. At this stage, the stirring blade maintains normal speed while the cutter rotates at low or high speed. If the cutting blade is not turned on or unable to reach the material, the granulation effect will be affected. Whether using a hydraulic or pneumatic spray gun, this process is usually completed within 5 minutes. If a pneumatic spray gun is used for atomization and adhesive addition, it can also be observed that due to the granulation effect, the particles become denser and the overall volume of the material is reduced. If the reduction exceeds one-third of the initial volume, it is necessary to consider whether the amount of adhesive used is appropriate. At the same time, attention should be paid to avoiding excessive adhesive that may cause particles to stick into layers under the stirring blade or on the pot wall, or situations where too many particles adhere to the stirring blade and cannot be removed.

Granulation stage

After the slurry addition is completed, start the mixing blade and set the cutting blade to low or high speed for granulation operation, with a duration of about 30 seconds to 5 minutes. This step aims to make the wet particles more uniform through the action of the cutting blade. It should be noted that there may be issues with poor material flow during the slurry addition stage, such as insufficient material participation in granulation in certain areas, or excessively wet adhesive spray points resulting in oversized particles. Through the granulation stage, the uniformity of wet particles can be further optimized.

Discharge whole granules

Most high shear wet granulators are equipped with a pelletizer at the discharge position. Although the granulation effect of the granulator may be relatively uniform, wet particles may aggregate into blocks under their own gravity. If not dealt with in a timely manner, these clumps will affect the drying efficiency in subsequent fluidized bed drying or oven drying processes, and may even form hard cores, thereby affecting dissolution. Therefore, it is necessary to equip a discharge granulator.

Spray principle

The nozzle is a key component of the spray system. There are currently over 20000 types of nozzles on the market, which can be divided into two basic structures: "single fluid" and "dual fluid". Single fluid nozzles mainly rely on hydraulic spraying, while dual fluid nozzles mix pneumatic and hydraulic, namely pneumatic spray guns (pneumatic type) and hydraulic spray guns (hydraulic type). The air pressure spray gun creates a local vacuum by compressing air, sucks in liquid, and atomizes it into small droplets; And hydraulic spray guns use compressed air to apply pressure to the adhesive solution, producing extremely small droplets. The main shapes of spray include fan, solid cone, hollow cone and liquid column.

Formation principle of fan nozzle spray:

The core theory of fan-shaped spray is "membrane cracking". When a high-pressure nozzle sprays liquid into the atmosphere, it forms a thin film as a whole. This film will first become flat due to vibration and then become unstable. Under the action of liquid surface tension, the shape of the film gradually evolves into a columnar shape and is eventually torn into droplets, which is called membrane fission. The diameter of the droplet will vary with the change of nozzle pressure. The formation of fan spray is attributed to the cat's eye structure and diffraction effect of the nozzle.

Spray forming principle of solid conical nozzle:

The core theory of solid cone spray is "internal flow channel". Inside the nozzle, some of the fluid is ejected after forced rotation, while the remaining fluid is directly ejected inside the nozzle. The combination of these two fluids produces a solid conical spray. Its internal x-shaped channel and fine orifice design ensure the accurate shape and correct angle of spray, and greatly reduce the possibility of blocking.

Spray forming principle of hollow conical nozzle:

The hollow conical nozzle uses the principle of centrifugal force for spray. After the liquid is introduced into the cyclone chamber, the centrifugal force of the vortex makes it diffuse and eject from the nozzle hole, thus forming a bell shaped hollow cone liquid film spray shape. This design produces a circular spray pattern. Its working principle is similar to putting water into a rotating container. Under the action of centrifugal force, the water is concentrated on the container wall, forming a hollow center, thus producing a hollow conical nozzle spray effect.