Advantages of one-step boiling granulator in the application of traditional Chinese medicine granules

The chemical properties of Chinese medicine are complex and diverse. We systematically analyze its properties and design a more reasonable one-step boiling granulation dryer for the current pharmaceutical industry in response to the existing problems. It includes centrifugal spray, boiling granulation, dry granulation, and micro-pellet granulation machine. It has good adaptability to materials with low softening points and strong hygroscopicity. And it can complete one-step granulation in terms of particle morphology, which greatly improves production efficiency compared to ordinary centrifugal spray drying followed by granulation. At the same time, it fully complies with GMP specifications and makes the equipment design more reasonable, scientific, environmentally friendly, and hygienic.

Chinese herbal medicines are extracted, concentrated and dried to make various granules, tablets, capsules and pills to meet the needs of different groups of people.

Traditional Chinese medicine granulation processing process:

   Traditional Chinese medicine formula granule process flow chart

In order to improve the yield of effective ingredients in Chinese medicine granules and make full use of medicinal resources, the extraction process usually uses a solvent that is 6-10 times the amount of medicinal materials, so that the concentration of the obtained extract is very small, with a solid content of about 2%. Therefore, it is necessary to add a concentration and drying step to compress the extract and remove the solvent. The granulation of Chinese medicine extract is the key to the entire process, and the quality of the granules will have a significant impact on the quality of the product.

Existing preparation methods and shortcomings of formulated granules

1. Centrifugal spray drying

In centrifugal spray drying, air is filtered and heated at the primary, secondary and high levels before entering the air distributor at the top of the dryer in a spiral tangent manner. The hot air enters the drying chamber in a spiral and uniform manner. At the same time, the liquid is atomized into 20-60μm droplets by the atomizer. When the droplets are in co-current contact with the hot air, they can be dried into powder products in a very short time. The dried powder is continuously output from the bottom of the drying tower and the cyclone separator. A small part of the powder enters the water foam dust removal spray and the exhaust gas is discharged by the induced draft fan.

The particles obtained by centrifugal spray drying are usually in the range of 200-400 mesh, which cannot meet the requirements of the formulation of granules. Later, granules need to be obtained through wet granulation, dry granulation, and boiling granulation processes.

The powder produced by spraying has problems such as wall sticking, agglomeration, poor fluidity, low yield, easy moisture absorption, and poor water solubility. A large amount of auxiliary materials such as dextrin need to be added during the drying process.

2. Wet granulation

After the powder is obtained by spray drying, it enters the high-speed mixer granulator for wet granulation, which requires the addition of a large amount of binder and wetting agent. Pure water and ethanol are commonly used.

Wet granulation requires the addition of a large amount of auxiliary materials, and the process is cumbersome, with exposure links, poor solubility of the finished product, uneven mixing, easy agglomeration, and low yield. It also requires secondary drying, screening and other steps......

3. Dry granulation

After the powder is obtained by spray drying, it is passed through a dry granulator to obtain the finished product. The dry granulator does not require a wetting agent or a binder, but only needs to mix the drug with the excipients and then directly granulate them through mechanical pressure.

The quality of dry granulation products is irregular, it is easy to have flowery materials, the yield is low, it needs to be returned for re-granulation, and it is easy to generate dust.

4. Boiling granulation

After the powder is obtained by spray drying, granules are obtained by a fluidized bed granulator.

After boiling granulation, unqualified granules need to be crushed and returned for further granulation. During the boiling granulation process, as the granules continue to grow, the equipment parameters need to be adjusted all the time, resulting in unstable equipment operation. In addition, batch equipment determines that the production line has low output, high energy consumption, large manpower expenditure, and high operating costs.

Ideal Chinese medicine formula granule equipment should have:

1. Yield: The yield of the spray dryer is only about 90%, and some materials are even lower. In addition, due to the loss of the back-end process, the overall yield of the entire production line is only about 80%. One-step granulation has no back-end process, and the overall yield of the product can reach more than 95%.

2. Cleaning: The spray tower has a large diameter and the equipment is high. The pipe diameter is also large and cannot be disassembled. It cannot be thoroughly cleaned, resulting in frequent bacterial contamination of materials. The one-step granulator has a compact structure, a small pipe diameter, and is easy to disassemble. It can be thoroughly cleaned.

3. System dust: In the multi-pass process after spray drying, the material will be exposed to the air, causing dust to fly. It does not meet the GMP production standards. The whole system of one-step granulation is in a closed state, and the whole process is isolated from the external environment. It is safer and more environmentally friendly.

4. Sticking to the wall: Sticking to the wall mainly occurs during the spray drying process. The material sticks to the tower wall, especially at the butt weld. This is the biggest drawback of spray drying. One-step granulation uses a two-fluid spray gun with a small atomization diameter, and the material is always in a boiling state. There will be no sticking to the wall phenomenon.

5. Floor space: The Chinese medicine extract spray dryer occupies a large area. A dryer with an evaporation capacity of ZPG350 has a diameter of 7 meters and a height of 15 meters, and there are multiple auxiliary machines. The space occupied by a one-step granulator with the same evaporation capacity is only about one-third of that of a spray dryer.

6. Particle shape: The powder produced by spray drying is 200-600 mesh, without particle shape, and needs to be granulated by the granulating equipment at the back end to obtain the desired particles. The particle shape of the one-step granulator is now mature, and various particles of four types, snowflake, golden sugar flat, spherical, and quasi-spherical, can be obtained. The fluidity, solubility, bulk density, porosity, etc. of the product can be adjusted.

7. Drug activity: The instantaneous temperature resistance of Chinese medicine extract is 120-240℃, and the long-term temperature resistance is 60-100℃. The long-term temperature resistance of some products is only 30-60 degrees Celsius, so low-temperature granulation must be used. The effect of temperature on drug activity is very obvious. The ideal state is to use dedicated equipment according to each different product. However, due to the wide variety of Chinese medicines, it is obviously impossible to achieve this. One-step granulation has the function of low-temperature granulation. And granulation and drying are achieved in one step. At present, this method can be maturely applied to avoid the production of dead particles and ensure high efficacy.

8. Equipment energy consumption: Compared with traditional spray drying, the air inlet temperature and material layer temperature of one-step granulation are relatively low. In addition, the heat utilization rate of one-step granulation is lower than that of spray drying. Taking ZPG350 as an example, the steam energy consumption of one-step granulation with the same evaporation capacity can be saved by more than 20%.

9. One-time finished product rate: The qualified rate of finished products produced by batch boiling granulator is about 70%, and the qualified rate of granules produced by one-step granulator can reach 85%. In addition, the remaining unqualified granules can be returned to granulation, and all qualified granules can enter the finished product warehouse, which improves production efficiency.

10. One-step granulation: One-step granulation is to add auxiliary materials to the concentrate or concentrate formula and then granulate to directly obtain the finished granules. Fully enclosed continuous production reduces the intermediate links such as spray drying and boiling granulation, and conducts fully enclosed continuous production. The process has no product exposure link and meets the GMP production standards. It adopts an intelligent centralized control system with simple operation. The entire production line only needs one controller and one inspector. The equipment runs stably.

Working process of one-step boiling granulator for Chinese medicine formula granules:

One-step boiling granulator flow chart