1. Process robustness:

Process robustness refers to the ability to minimize changes in control parameters and personnel intervention from the beginning to the end of the process. This ideal state requires comparison in all aspects to be achieved. Like the problem that continuous process validation aims to solve, if a prescription has defects from the beginning of the process flow, it is also difficult to hope for compensation through coating.

There are relatively many processes involved in solid dosage forms, and sometimes there is a dependency mentality. For example, if the properties of raw materials change and the granules produced during granulation are not good, granulation may want to adjust the tablet pressing process to solve the problem. If the resulting core is not good due to poor granules, tablet pressing may want to adjust the coating process to solve the problem. However, the problem is that coating is not a process and cannot cover up all defects. Often, coating failure actually starts from granulation. Therefore, process robustness is the foundation, and the following content will be optimized on this basis.

2. Product loading capacity:

It is generally described that the loading capacity is not allowed to expose the baffle in the spray area. There is no doubt that the baffle and other stainless steel parts are cold and dry slowly, and it is easy to cause adhesion when sprayed on them. In order to improve coating efficiency, the loading capacity should be as much as possible (as long as the tablets do not fall out). Too little loading capacity can cause uneven sliding of the tablet bed and coating. It should be noted that the loading capacity should ensure that the exhaust chamber can be covered after the formation of a uniform waterfall in the tablet bed, otherwise reactive hot air will reduce drying efficiency and prolong coating time. Of course, there is also a type of 'shoe' coating machine that can adjust the size of the exhaust chamber to solve this problem.

3. Coating pot speed:

There is an experiment that examines the relationship between rotational speed and coating uniformity. In the experiment, it can be observed that the thickness of the bread coating is greater than the diameter surface, and the diameter surface is greater than the edge where the two meet. Considering the difficulty in observing the edges, it can be seen that increasing the rotational speed reduces the sliding of the tablet bed and improves the waterfall flow, resulting in a more uniform coating. However, excessive rotational speed can also lead to increased wear.

There are many parameters that affect the speed setting, such as core size and shape, core brittleness and smoothness, baffle, loading capacity, drying ability, etc. The size, shape, and smoothness of the core, as well as the shape of the baffle, have an impact on the formation of waterfall flow in the bed. Flat surface cores may sometimes form twin or even multiple cell bodies due to delayed drying. Of course, adding a small curvature to the core plane can solve this problem.

It is not difficult to understand the brittleness of the chip core. If the brittleness is poor, too fast a rotation speed can lead to the production of edges, fragments, etc. When the loading capacity of the chip is small, in order to compensate for the sliding of the chip bed, the speed can be improved by increasing it. In addition, the drying speed and drying capacity of the coating process also affect the speed. If the drying speed is slow, it can be improved by reducing the spray volume and decreasing the speed to increase the drying time. Therefore, selecting a low speed that can create a waterfall flow in the bed is sufficient.

4. Spraying range and spray distribution:

The spraying range is directly related to the design of the spray gun, and the quantity, installation angle, and installation distance will all have a direct impact. Compared spray guns can generally ensure the relatively uniform distribution of droplets in the whole spray area, and the current effect in China is slightly worse. For the current common multi gun design coating machine, attention should be paid to avoid overlapping or leaking points in the middle of the multi gun spray area, which will affect the uniformity of the coating layer, and of course, prevent spraying on the boiler wall.

There is no clear value for the height of the spray gun. Generally, the film coating should be 30cm above the tablet bed, while the enteric coating can be lower. The angle of the spray gun should be perpendicular to the tablet bed after forming a waterfall to prevent the coating liquid from rebounding. There is no clear indication as to whether the spray gun should be installed in the center or the upper one-third of the bed. Both positions are acceptable, and relatively speaking, installing it in the upper one-third can take longer drying time.

5. Flow rate of coating solution:

Peristaltic pumps are widely used for conveying coating liquids due to their good flow control ability and pollution-free advantages. However, in practical applications, it can be found that the delivery volume of coating liquids varies greatly and is not uniform at low rotational speeds. In an ideal situation, in order to obtain a relatively stable flow rate, the pump speed of a peristaltic pump can be set to the middle of the range. For example, for a peristaltic pump with 0-200 revolutions per minute, using a pump speed of about 100 can achieve good flow control effect. If not applicable, a pump head with a thinner diameter can be used.

For the coating machine with individual liquid delivery for each spray gun, if the rubber hose needs to be replaced, all the pipes of the same pump head should be replaced. There is a case where the effectiveness of a stable coating machine decreased after replacing one of the hoses. After investigation, it was found that there was a difference in elasticity between the new and old hoses, resulting in a change in the flow rate of the coating solution.

6. Drying:

For the drying process of coating, air volume is more important than temperature, which is also the main source of performance differences between domestic and foreign equipment. It should be noted that the negative pressure control formed by the air inlet and exhaust is not that the greater the negative pressure is, the better. If the negative pressure is too large, the air leakage at the feeding door will affect the spray effect. Therefore, it is recommended to use a smaller negative pressure or even a negative pressure. In addition, in recent years, with the promotion of water-based coating, many people have mistakenly used the coating temperature as the inlet air temperature. For example, the coating temperature of 40 ℃ suggested by Kalekang refers to the bed temperature, and even if the inlet air temperature is 70 ℃, it does not affect it. Of course, measuring the bed temperature should try to test the middle area just after spraying.

For the drying process, preheating can achieve better drying effect and improve coating efficiency. Compared with foreign product cores, preheating is generally beneficial for improving efficiency. However, preheating many cores in China may lead to adverse consequences such as decreased brittleness (such as some traditional Chinese medicines). Therefore, preheating is not mandatory and should be determined based on the core's ability.

7. Core for coating:

For example, the mechanical integrity, film adhesion, marking (scoring), and film uniformity of the tablet core. For the tablet core, brittleness is more important than hardness. It is recommended that the brittleness of the tablet core be less than 0.5% and not more than 0.1%, with a hardness of 8-10Kp. Of course, this is only an ideal recommended value. In fact, many tablets with a hardness of 4Kp can also be coated. The adhesion of the tablet itself depends on the porosity, theoretically microcrystalline cellulose>lactose>sucrose>calcium hydrogen phosphate. (PS: I have seen a prescription before where the adhesion of the coating is poor. Adding a small amount of sugar to the coating can improve adhesion.) If the compression mold is worn, causing the core of the tablet to have grooves or burrs, the coating liquid is not easy to cover during the coating process or the burrs fall off during the coating process, which can also affect the uniformity of the coating.

If it is a scoring sheet, it is also necessary to analyze the easily worn areas based on the sheet shape, and avoid or adjust them during scoring. In addition, the formula of the tablet core also has a significant impact on the coating effect, such as magnesium stearate. Magnesium stearate has a sheet-like appearance, and the lubrication mechanism is to wrap around the surface of the particles. Therefore, the mixing time of magnesium stearate should not be too long, 1-2 minutes is sufficient. Excessive dosage or prolonged mixing time may cause the core to become soft, resulting in decreased compressibility, dissolution, and film adhesion (this has a greater impact on plastic deformation materials such as MCC or compressible starch, and a slightly smaller impact on brittle deformation materials such as lactose, where brittle fracture increases the contact area). In addition, super disintegrants may cause uneven pits on the surface after coating, because the mechanism of action of super disintegrants is water absorption and expansion, which is caused by super disintegration and moisture absorption during the coating process.