In the production process of solid preparation, the phenomenon of separation of different particles in the uniformly mixed powder is very common. Understanding the mechanism of separation is of great help to the assessment and control of production process risk. The author has translated the relevant contents of the powder separation mechanism for readers' reference.
General separation mechanism of (I) powder
"Separation mechanism" refers to the mode of separation of a mixture or the driving force that causes the separation of the components of a mixture. Although there are many different separation mechanisms that can adversely affect the homogeneity of the mixture, in the pharmaceutical industry, three separation mechanisms are of primary concern for mixing process operations. The three separation mechanisms are as follows:
1.Sieve separation (sometimes referred to as "osmotic separation");
2.Fluidic separation (sometimes referred to as "air introduction");
3.fugitive dust separation (sometimes referred to as "particle inclusion in the air stream").
These three mechanisms will be described in detail below. It should be noted that the above three terms are not universal definitions. The separation may be due to one of the above mechanisms or a combination of several mechanisms.
Material properties that (II) affect separation
Whether separation occurs, to what extent, and by what mechanism, depends on the nature of the mixture and the process conditions to which the mixture is subjected. Material properties that affect the separation tendency are mainlyThere are some of the following:
1,APIThe average particle size and particle size distribution of the particles in the auxiliary material and the final mixture: any mixture of average particle size may be separated, but different particle sizes may be dominated by different mechanisms;
2Particle density: particle density affects how the mixed components flow;
3Particle shape: Compared with particles with irregular shapes, spherical particles have stronger mobility, so they are more likely to be separated;
42. Particle elasticity: This property will affect the collision between particles and the surface, resulting in the accumulation of components in different places when filling the storage tank or during the tabletting process;
5The cohesive strength of the mixture: In general, the greater the cohesive strength of the mixture, the less prone to separation. However, as long as enough energy is given to expand the mixture, or to separate the particles, even materials with high cohesive strength can be separated;
6Electrostatic effects: The ability of components to generate and maintain static electricity, as well as the binding force to surfaces or other excipients, can also cause a tendency to separate.
Among these factors listed above, the separation caused by particle size is the most common situation at present. In fact, as will be discussed below, particle size is the most important factor affecting the three separation mechanisms discussed herein.
（III) Screening and separation
For many industrial processes, screening separation is very common. Under the right conditions, fine particles tend to be sieved or permeated by coarse particles. For separation to occur under this mechanism, the following four conditions must be met:
1The particle size range must be met. Typically, the minimum ratio of different average particle sizes between components is1.3:1;
2The average particle size of the mixture must be large enough, usually greater than about.100μm;
3The mixture must flow relatively freely, which allows the particles to move;
4There must be relative movement between particles, which is very important. If there is no relative movement of particles, even if the separation trend is very high and the mixture of excipients meets the above three conditions, separation will not occur. There are many ways to induce relative motion, such as the formation of accumulations when filling the material tank, the vibration of surrounding equipment (e. g., tableting equipment), or the tumbling and sliding of particles as they pass through a slope.
If any of the above conditions does not exist, then separation under this mechanism will not exist.
The result of the sieving separation in the storage tank is usually an "edge-to-edge" variation in particle size distribution. Particles of small size are enriched below the addition port, while coarse particles are partially enriched at the edge of the pile.
Figure1. sieving separation2dimensional profile (the particle size of the black particles is approximately1200μmThe size of the white particles is about350μm）
(IV) fluidized separation
If the treated powder can be fluidized, a change in particle size or density will generally result in separation of the material in the vertical direction. Fine or light powder is usually enriched on large particles or more dense particles. This separation may occur when filling a tank or other pipeline. Separation may also occur when mixing is stopped in the mixing tube.
Fluidic separation often results in a gradient distribution of fines and coarse powder in the vertical direction. The fines can still flow for a period of time after mixing or filling is stopped. In this fluidized state, larger and/Or more dense particles tend to settle at the bottom. When the bed of material is degassed, the fines are reached to the surface by the escaping air. For example, when the material tank is quickly filled, the coarse particles will move downward through the gas-filled material bed, while the fine powder is still in a fluidized state, in a near-surface position. If the material is fluidized during mixing, this separation can also occur after mixing has stopped.
The material contains a certain proportion of particle size less100μmof particles, the phenomenon of fluidization is common. Fluidic separation is most likely to occur when air drives fine powder materials, when materials are discharging or filling at high speed, or when there is a cross-flow. As with the screening separation mechanism mentioned in the previous section, the greater the cohesive energy of the material, the less likely it is to separate by this mechanism.
The reason for the fluidization of the gas flow is that the exhaust gas during the transfer of the material is not sufficient. For example, the material discharge from a flip mixer is added to a material tank, which is sealed by an air seal.. When the mixed material is transferred from the mixer to the material tank, the air in the material tank is disturbed and a slight vacuum is formed in the mixer. If the ventilation between the two is normal, the air overflows from the material tank, separates from the material and enters the mixer. If both are poorly ventilated, air must pass through the material flowing from the mixture to the material tank. In this case, the fines are carried away from the mixture and onto the surface of the blender material.
Figure2. Fluid separation occurs when the material in the mixer is added to the storage tank.
(V) dust separation
Similar to fluidized separation, when dealing with fine, free-flowing particle sizes of less than about50μmIn the case of powder, dust is the most likely problem, and it may also occur in other particle size ranges. When filling the tank, if dust is present, the air flow driven by the flowing material may carry the particles away from the filling point. The location of dust retention is controlled by the sedimentation rate of the particles. The diameter of the particles has a more significant effect on the sedimentation rate than the density of the particles.
Give an example of this mechanismPour a mixture of fine and coarse particles into the center of the storage tank. When the material flow impacts the material pile in the storage tank, the air column moving with the material flow is deflected. The air swept through the pile of material and moved to the edge of the storage tank. In the process, the airflow became chaotic. After this, the air moves back to the wall of the tank, usually in the form of a vortex. At this time, the velocity of the air is low, which allows many particles to fall out of suspension. The finest particles (with the lowest settling rate) are brought to the edge of the storage tank because the settling rate is greatly affected by the particle size. Larger particles will be concentrated at the filling port because the air flow is strong enough to prevent fine particles from depositing here. Dust separation is more likely to lead to unpredictable separation patterns, depending on how the storage tank is filled, the ventilation in the storage tank and the use and installation of the dust collector.