Discussion on Dry Granulation Technology

Overview

Dry granulation is a method in which drugs and diluents, disintegrants, lubricants, etc.

The production of solid preparations is still the most common in the production of pharmaceutical products, but some products have poor material fluidity, so they must be granulated to improve the fluidity of the materials.

The purpose of dry granulation is generally to improve the fluidity of materials, eliminate degradation caused by wet granulation to improve product stability, prevent delamination between materials, and increase bulk density.

Compared with the more mature wet granulation technology, dry granulation technology has many advantages, but there are also some problems.

Advantages and disadvantages of dry granulation

1.

Dry granulation is a process of agglomeration.

Generally speaking, one of the main advantages of dry granulation over wet granulation is that it does not require water or any organic solvents.

For drugs or excipients that have poor fluidity or are sensitive to heat or moisture, dry granulation technology can be used.

2.

(1) Leakage of uncompacted materials or fine powder

First, use a gravure roller for sealing, because the leakage between the seal rings on the roller side will produce uncompacted material.

(2) Material compressibility loss

The loss of material compressibility is a common problem in dry granulation, which is more obvious under higher rolling pressure.

(3) Material sticking roller

Lubricants can be added to control the moisture content of the material within the optimal range.

(4) Suppression of strips and stratification

Control the consistency of the particle size distribution, density and other properties of the material to reduce stratification.

Factors affecting dry granulation

1.

(1) Compressibility: Compressibility is an important factor to ensure that the material can be compressed into strips.

(2) Moisture: When the moisture content of the material is too high, the phenomenon of sticking may occur during the rolling process, and when the moisture content is too low, the material may not be easy to be pressed into strips.

(3) Material viscosity: viscosity refers to the ability of materials to bond and polymerize.
Dry granulation materials must control their viscosity range.

2.
The influence of equipment parameters on dry granulation

Generally, feeding speed, roller pressure, and roller speed have a greater influence on dry granulation.
The order of the magnitude of the impact on the particle yield and friability is: roller speed> roller pressure> horizontal feeding speed.
The particle yield is positively correlated with roller pressure and horizontal feeding speed, and negatively correlated with roller speed.
The fragility of particles is the opposite.

Precautions for dry granulation

Considering the complexity of dry granulation, developing a dry granulation process for medicines is not always a simple task.
Here, some key considerations are summarized, and I hope it will be helpful to everyone in the development of dry granulation technology.

1.
The design of the experiment should consider the mechanical properties of the material.
For example, even under low pressure, the material can be significantly formed into strips.
If this material is used for dry granulation in a relatively high pressure range, the influence of dry granulation pressure on the stripe characteristics of the material and the compressibility of the particles may not be observed.

2.
The dry granulation process is continuous.
Should the material leaking through the roller be recycled? Recycling can maintain high yields to reduce costs, but it can also lead to poor particle fluidity.

3.
The way of using lubricant, that is, internal lubricant and external lubricant.
Different methods may cause significant difference in material properties.
Compared with external lubricant, internal lubricant often shows worse tablet performance.
Pressure.
This requires careful consideration and evaluation in the process and formulation design process.
Generally speaking, it is best not to use lubricants unless you need to handle the powder, for example, to avoid the powder sticking to the rollers.

4.
The strips produced on the dry granulator usually show uneven density distribution.

5.
Although dry granulation is used to improve the fluidity of other powders with poor fluidity, the fluidity of the starting powder must meet the requirements, so that the dry granulation feeding process can proceed smoothly.

Rules to be observed in dry granulation

1.
Control the porosity of material strips

The porosity of the material strip is a key parameter to control the quality of the material strip and the successful amplification of the material.
For a given powder mixing prescription, the porosity of the material strip is mainly determined by the roller pressure, the roller gap and the feeding frequency.
By changing these parameters, material strips with the same porosity can be obtained on different dry granulators.

2.
Avoid excessive compaction of materials

We need to control the required pressure to a minimum to obtain the required particle size distribution and fluidity bands.
Over-compacted strips tend to produce particles that are less compressible, because these particles are not easily deformed during the tableting process.
In addition, the sizing process parameters should be optimized to obtain particles with consistent particle size distribution to ensure particle fluidity and tableting stability.

3.
Use small particles of starting materials

The particle size of the starting material will affect the final tensile strength of the tablet after dry granulation.
Under normal circumstances, the smaller the binder particles of the same material, the better the tableting performance.
However, the proportion and size of the fine particles should not be too extreme, so as not to have a negative impact on the fluidity of the powder, which is very important for the material feeding in the dry granulation process.

4.
Balance the mechanical properties of starting materials

The initial material should maintain a reasonable balance between ductility and brittleness.
In the granulation process, more plastic materials tend to be more sensitive to changes in parameters, such as changes in roller pressure, lubrication time and strength.
When fragile materials are compressed, higher pressure is required.

Commonly used auxiliary materials in dry granulation

The key of dry granulation is the adhesion between particles, so the material must have a certain degree of adhesion and compressibility.
Therefore, the auxiliary materials can be selected according to their adhesiveness and compressibility.
In dry granulation, the material is usually composed of a mixture with poor compressibility and good compressibility in order to obtain a band-like substance with sufficient mechanical strength to produce The particles that meet the demand.

Below I introduce several excipients suitable for dry granulation.

Microcrystalline cellulose: Because microcrystalline cellulose has hydrogen bonds, the hydrogen bonds will associate after pressure, so it has good compressibility and can be used as a binder during dry granulation.

Compressible starch: Compressible starch has good compressibility and fluidity, and has a certain disintegration effect after being compressed into tablets, so compressible starch is also used more in dry granulation.

Lactose, dibasic calcium phosphate, some compound auxiliary materials (such as cellulose lactose), etc.
can also be used in dry granulation.

references

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Roll compaction/dry granulation: pharmaceutical applications[J].
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[3] Sun CC, Kleinebudde P.
Mini review: Mechanisms to the loss of tabletability by dry granulation[J].
European Journal of Pharmaceutics & Biopharmaceutics, 2016:9-14.

[4] Zhang Qingling, Luo Youhua, Xu Guanghui, et al.
Application of dry granulation process in the preparation of oral solid preparations of traditional Chinese medicine[J].
China Modern Chinese Medicine, 2020(5).

[5] Li Hongcheng.
Application progress of dry granulation technology in drug research [J].
China Pharmaceuticals, 2013, 22(006): 127-128.