Causes And Solutions Of Fragments In Solid Dosage Research

The tablet is split from the waist during the pressing process or subjected to vibration or after being placed, which is called lumbar crack; the top crack is called top crack, and the waist crack and top crack are collectively called lobes. After the lobes are produced, the surface of the tablet will be rough, and the dose will be inaccurate, which will affect the quality of the tablet. Fragmentation may occur during tableting or after a period of time, so check the friability immediately after tableting, or use other simple methods, such as dropping the tablet from a height of 1 meter on a hard floor , or take a few pieces in the palm of your hand, put your hands together, shake it vigorously several times, and check whether there are lobes.

Part 1 Causes And Solutions Of Fragmentation

After the crack phenomenon occurs, the following aspects should be considered emphatically:

1.1 Raw Materials

The raw material itself has poor compressibility and a large drug loading capacity. The compressibility of raw materials is related to its own crystal form. Generally, crystals belonging to the cubic system can be directly compressed into tablets; while scale-shaped, needle-shaped and spherical crystals are not easy to directly compress into tablets, they should be crushed into fine powder and then wet granulated. Compress the tablet, otherwise, slivers, loose tablets, etc. will easily occur during the tablet compression.

Solution:

For granules that are completely dry or lack of water, according to the nature of the drug itself, natural moisture absorption or spraying with ethanol at an appropriate concentration can be used. For example, drug granules containing crystal water can be solved by this method when the crystal water loses too much shards, loose tablets, and slow disintegration.

However, some drugs are highly viscous, and when sprayed to absorb moisture, they tend to stick into lumps, and the hardness is not uniform, which will cause problems such as unstable tablet weight and damage to the tablet press. In this case, natural moisture absorption or re-granulation is better.

1.2 Excipients

Improper or insufficient amount of binder and wetting agent, insufficient adhesive force of the binder in the granules, too coarse, too fine or too much fine powder, so that the capacity filled in the die hole is too uneven. In addition, excessive lubricant can also cause splinters.

Solution:

The purpose of reducing the degree of elastic recovery of particles and increasing the ability of plastic deformation can be achieved by adding plastic materials. For example, compressible starch, lactose, crystal cellulose, and pregelatinized starch are all excipients with relatively good plastic deformation ability.

1.3 Preparation Process

During the tablet compression process, due to the high speed of the tablet press, the particles containing more fine powder cannot be discharged in time during the compression process. When the pressure is released, the air inside the tablet expands, and the elasticity returns to form lobes.

Solution:

On the premise that the disintegration time limit is qualified, use a more viscous binder to increase the concentration of the binder solution and reduce the generation of a large amount of fine powder. Install the pre-compression cam on the tablet press and use secondary compression. When the pre-compression cam performs pre-compression, it can remove part of the air contained in the fine powder, and when the die moves to the bottom of the final pressure roller, it will be compressed and formed.

Appropriately reduce the tablet pressing pressure of the tablet press, reduce elastic internal stress, reduce its elastic recovery rate, and at the same time appropriately slow down the tablet pressing speed. Sieve off part of the fine powder and reduce the amount of lubricant appropriately. In addition, it should be noted that the particles should be mixed evenly to avoid cracks caused by uneven mixing.

1.3.2 The Granules Are Too Dry, And The Drug Containing Crystal Water Loses Too Much, Resulting In Shards.

An appropriate amount of moisture in the granules can increase the plastic deformation of brittle particles, reduce elasticity, and enhance tablet hardness, which is the basic condition for tablet compression; if the moisture content is too low, the viscosity between materials will be reduced during tablet compression, forming If the particle strength is insufficient, it is easy to produce capping after pressurization. However, if the water content of the granules is too high, the tablet hardness will also be reduced.

Solution:

In the process of process touch, the appropriate water content range of the tablet granules is obtained through the water content investigation and test, and the water content of the granules is controlled within the appropriate range by parameters such as drying temperature, time and ambient humidity.

1.4 Equipment Machinery

1.4.1 The pressure of the tablet press is too large, and it will be broken due to the strong rebound force.

Solution:

Properly adjust the pressure to reduce the elastic internal stress.

1.4.2 Excessive Speed

Solution:

Properly slow down the speed and prolong the compression time.

1.4.3 The Die Does Not Meet The Requirements, The Punch Has Length, The Middle Part Is Worn, The Middle Part Is Larger Than The Upper And Lower Parts Or The Punch Is Curled Inward

After the die has been used for a period of time, it gradually wears out, so that the upper punch does not match the die ring and the punch is curled inward, and the pressure is uneven, which causes the tablet part to be over-pressed and cause capping. When the die ring is used for a long time, the middle of the die hole increases due to friction, so that the diameter of the middle is larger than the diameter of the mouth, which will also split when the tablet is ejected.

Solution:

Improve the matching of punching dies, check and replace them in time.

1.5 Environment

The room temperature of the tablet pressing room is low and the humidity is low, which is easy to cause cracks, especially for drugs with poor viscosity.

Solution:

Adjust the ambient humidity and temperature.

Part 2 Conclusion

Splitting is one of the common problems in tablet production. In order to solve this problem, foreign researchers have discussed the mechanism of lobes from different aspects. Some researchers believe that lobes are related to the compressibility of materials under pressure and their compression behavior under pressure. Some people also think that it is due to the uniaxial tension generated during the decompression process after the tablet is pressed, and the split phenomenon can be avoided if the triaxial decompression is performed simultaneously. Some scholars have also investigated the stress concentration problem of compression materials. However, due to many factors affecting the lobes, there is no conclusion that can fully reflect the lobes.