Analysis and solution to problems in the tableting process

Pine slice

After the tablet is pressed, the hardness is not enough, the surface has pitting holes, and the finger is gently pressed and broken, the cause analysis and solution:

1 The pulverization fineness of the drug is insufficient, the fibrous or elastic drug or the oil component is contained in a large amount and the mixing is uneven. It can be overcome by pulverizing the drug through a 100 mesh sieve, selecting a binder with a strong viscosity, appropriately increasing the pressure of the tablet press, and increasing the mixing of the oil drug absorbent.

2 The amount of adhesive or wetting agent is insufficient or improperly selected, so that the granular texture is loose or the particle thickness is unevenly distributed, and the coarse particles and the fine particles are layered. It can be overcome by selecting appropriate binders or increasing the amount, improving the granulation process, mixing the soft materials, and mixing the particles.

3 The water content of the particles is too small, the excessively dry particles have greater elasticity, and the drug containing crystal water loses more crystal water during the drying process of the particles, making the particles crisp and easy to loosen the pieces. Therefore, when granulating, the water content of the granules should be controlled according to different varieties. If the prepared granules are too dry, spray an appropriate amount of dilute ethanol (50% - 60%), mix and compress.

4 the nature of the drug itself. Although the tablets with high density have a certain hardness, they cannot withstand collision and shaking. For example, bismuth nitrate tablets and soda granules tend to produce pine flakes; the density is small, the fluidity is poor, the compressibility is poor, and the granulation is re-granulated.

5 The flowability of the particles is poor, and the particles filled in the die holes are not uniform.

6 There are large pieces or particles, debris blocking the scraper and the discharge port, affecting the filling amount.

7 factors of tableting machinery. The pressure is too small, the punching machine punches are not uniform, the speed is too fast or the granules in the hopper are added for a long time. It can be adjusted by adjusting the pressure, checking whether the die is complete, adjusting the speed of the car, and adding particles to keep a certain amount of stock in the hopper.

2. Splinter

When the tablet is shaken or placed, there is a split from the waist called the lumbar split; the split from the top is called the split, the lumbar split and the split is called the split, the cause analysis and solution:

1 The drug itself is more elastic,

Fibrous drugs or more oil-containing ingredients.

Sugar powder can be added to reduce fiber elasticity.

Strengthen the adhesion or increase the absorbent of the oily drug, mix well and compress.

2 Adhesive or wetting agent is improper or insufficient, and the adhesion of the particles is good when pressed.

3 The granules are too dry, and the crystallization water-containing drug loses too much to cause lobes, and the solution is the same as that of the pine slices.

4 Some crystalline drugs have not been fully comminuted. Such drugs can be sufficiently pulverized and granulated.

5 too much fine powder,

a split caused by excessive lubricant,

Part of the air in the powder cannot escape in time and is pressed into the tablet.

When the pressure is released,

The air inside the tablet expands to cause a split,

It can be overcome by sieving off some of the fine powder and appropriately reducing the amount of lubricant.

6The pressure of the tablet press is too large, the fan has large elasticity and splits; the speed is too fast or the die does not meet the requirements, the punch has a length, the middle die hole is worn, the middle part of the middle die is larger than the upper part or the punch is curled inward, which can make The lobes are caused when the tablet is ejected.

Adjustable pressure and speed, improve die matching, and timely check and exchange.

7 The tableting chamber has low room temperature and low humidity, which is easy to cause lobes, especially for poorly viscous drugs. Adjusting the air conditioning system can be solved.

3. Sticking and rushing

When the tablet is pressed, the fine powder on the surface of the tablet is adhered by the punch and the die, so that the sheet surface is not only uneven, and the unevenness is uneven, and the lettering punch is more likely to be stuck. The edge of the slanting edge is rough and grainy. Reasons and solutions:

1 The particles have too much water content, contain hygroscopic moisture-sensitive drugs, and the operating room temperature and humidity are too high to cause sticking.

Care should be taken to properly dry, reduce the temperature and humidity of the operating room, and avoid moisture in the dampening drug.

2 The amount of lubricant is too small or unevenly mixed, and the fine powder is too much. The amount of lubricant should be appropriately increased or mixed thoroughly to solve the problem of sticking.

3 The surface of the punch is not clean, there is anti-rust oil or lubricating oil, the surface of the new die is rough or the lettering is too deep and angular. The punch can be wiped clean, replaced with a substandard die or rubbed with a trace of liquid paraffin on the surface of the lettering punch to lubricate the surface. In addition, if it is caused by mechanical heating, check the cause and repair the equipment.

4 The punch and the die are too tight to cause the slamming. The supporting inspection of the die should be strengthened to prevent hoisting.

4. The difference in slice weight exceeds the limit

The difference in finger weight exceeds the limits set by the Pharmacopoeia, causing the cause and solution:

1 The particle size distribution is uneven, and the particle flow rate is different when the tablet is pressed, so that the thickness of the particles filled in the die hole is not uniform. For example, if the amount of coarse particles is large, the film is light, and if the fine particles are large, the tablet weight is heavy. The granules should be mixed or sieved to remove too much fine powder. If it cannot be solved, it should be regranulated.

2 If the fine powder adheres to the punch and causes the difference in the weight of the film to be large when the lifting is performed, the undershooting rotation is not flexible at this time, it should be checked in time, the die is removed, and the undercut and the die hole can be cleaned.

3 The flowability of the particles is not good, and the amount of particles flowing into the die holes is often too small, causing the difference in the weight of the tablets to be too large and excessive. The granulation should be re-granulated or a suitable glidant such as micro-silica gel should be added to improve the fluidity of the particles.

4 The hopper is blocked, and this phenomenon often occurs in drugs with strong viscosity or moisture permeability. The hopper should be dredged, the tableting environment should be kept dry, and the glidant should be added as appropriate.

5 The punch has poor adhesion to the die hole. For example, more powder is leaked between the outer periphery of the undershoot and the wall of the die hole, causing the phenomenon of "squeaking" of the undershoot, resulting in insufficient material filling. The punch should be replaced in time. Medium mode.

6 The speed is too fast and the filling amount is insufficient.

7 The length of the first rush is different, resulting in different fillers.

8 The feeder is not installed in place, resulting in different packing.

5. Disintegration delay

It means that the tablet can not complete the disintegration within the prescribed time limit, which affects the dissolution, absorption and exertion of the drug. The causes and solutions are as follows:

(1) Effect of tablet pore state The penetration of water is the primary condition for tablet disintegration, and the speed of water penetration is related to the many pore states inside the tablet. Although the appearance of the tablet is a compact sheet, it is actually a porous body, which has many pores inside and is connected to each other to form a network of capillaries which are twisted and twisted, interlaced, and closed. The type is also open. The water enters the inside of the tablet through these pores, and the law can be explained by the following capillary theory: L2=Rγcosθ/2η·t The above formula is the law of liquid flowing in the capillary, where L is liquid transparent. The distance into the capillary, θ is the contact angle of the liquid with the capillary wall, R is the pore diameter of the capillary, γ is the surface tension of the liquid, η is the viscosity of the liquid, and t is the time. Since the general disintegration medium is water or artificial gastric juice, its viscosity does not change much, so the four main factors affecting the penetration medium (moisture) into the tablet are the capillary number (porosity) and the capillary pore diameter (pore diameter R). The surface tension γ of the liquid and the contact angle θ.

The conditions that affect these four factors are:

1 The compressibility of the raw materials.

When the compressible raw materials are compressed, they are prone to plastic deformation. The porosity and pore diameter R of the tablets are small, so the amount of water penetration and the distance L are relatively small, and the disintegration of the tablets is slow. Experiments have shown that the addition of starch to certain tablets tends to increase the porosity and significantly increase the water absorption of the tablet, which is beneficial to the rapid disintegration of the tablet. However, it cannot be concluded from this that the more starch, the better, because the starch is too much, the compressibility is poor, and the tablet is difficult to form.

2 hardness of the particles.

When the hardness of the granules (or materials) is small, it is easily broken due to pressure, so the compressed tablet pores and

The pore diameter R is small, so the amount of water penetration and the distance L are also relatively small, and the tablet disintegration is also slow; otherwise, the disintegration is faster.

3 tableting force.

Under normal circumstances, the greater the pressure, the smaller the porosity and pore diameter R of the tablet, the smaller the amount of water permeation and the distance L, and the slower disintegration of the tablet. Therefore, the pressure at the time of tableting should be moderate, otherwise the tablet is too hard to be disintegrated. However, some tablets have a disintegration time that is shortened with an increase in pressure. For example, phenacetin tablets use starch as a disintegrant. When the pressure is small, the porosity of the tablet is large, and the disintegrant absorbs water. There is sufficient room for expansion, and it is difficult to exert the effect of disintegration. When the pressure is increased, the porosity is small, and the disintegrant has sufficient room for expansion after water absorption, and the tablet collapses and disintegrates faster. Lubricants and surfactants. When the contact angle θ is larger than 90°, cos θ is a negative value, and moisture cannot penetrate into the pores of the tablet, that is, the tablet cannot be wetted by water, so that it is difficult to disintegrate. This requires the drug and the excipient to have a small contact angle θ. If the θ is large, for example, the contact angle θ of the hydrophobic drug aspirin is large, an appropriate amount of the surfactant is added to improve the wettability and reduce the contact angle θ. The value of cos θ is increased to accelerate the disintegration of the tablet. Hydrophobic lubricants commonly used in tablets may also seriously affect the wettability of the tablet, increase the contact angle θ, and make it difficult for water to penetrate, resulting in slow disintegration. For example, magnesium stearate has a contact angle of 121°. When it is mixed with the granules, it will adsorb to the surface of the granules, so that the hydrophobicity of the tablet is remarkably enhanced, so that the water is not easily penetrated, and the disintegration becomes slow, especially hard. When the amount of magnesium sulphate is large, the phenomenon is more obvious. Similarly, when the hydrophobic lubricant is mixed with the granule for a long time and the mixing strength is large, the surface of the granule is covered with a hydrophobic lubricant.

Therefore, the pore walls of the tablet have a strong hydrophobicity, so that the disintegration time is significantly prolonged. Therefore, in the production practice, the variety, dosage, mixing intensity and mixing time of the lubricant should be strictly controlled to avoid a large amount of waste.

(2) Impact of other excipients

1 binder. The greater the adhesion, the longer the disintegration time of the tablet. In general, the order of viscosity of the adhesive is: animal

Glue (eg gelatin) > gum (eg gum arabic) > syrup > starch slurry. In specific production practices, tablets must be put

The molding is combined with the disintegration of the tablet, and an appropriate binder is used together with an appropriate amount.

2 disintegrant. For the current domestic disintegrant varieties, it is generally believed that the disintegration degree of low-substituted hydroxypropyl cellulose (L-HPC) and sodium carboxymethyl starch (MS-Na) can meet the requirements of the pharmacopoeia, dry starch The actual situation as a general application of disintegrants is not contradictory, because dry starch is a good disintegrating agent because it can meet the requirements of the pharmacopoeia, and the dry starch is cheap and easy to obtain. In addition, the disintegration agent is added in different ways, and different disintegration effects are also produced.

(3) Effects of tablet storage conditions

After the tablets are stored, the disintegration time tends to be prolonged, which is mainly related to the temperature and humidity of the environment, that is, the tablets are slowly wet.

The disintegrating agent is prevented from exerting its disintegration action, and the disintegration of the tablet is thus relatively slow.