Tablet Production Process Technology, Flow And Clean Area Division

Part 1 Tablet Overview

Tablets refer to medicinal material extracts, medicinal material extracts plus medicinal material fine powders into medicinal material fine powders and suitable excipients mixed and pressed in the form of discs or special-shaped tablets, including extract tablets, semi-extract tablets and whole powders piece. Tablets are solid drug-containing preparations made by compression or molding, with or without diluents. Tablets have been widely used and have remained popular since the 19th century.

Although the basic operating method of tablet production has remained the same, the tablet manufacturing process has been greatly improved. Efforts are ongoing to further understand the physical properties of powders and factors that affect the bioavailability of dosage forms after oral administration. Equipment has been continuously improved, such as tableting speed and uniformity of tableting.

Tablets can be round, oval, rectangular, cylindrical or triangular, although they often vary in shape. Tablets vary widely in size and weight, depending on the dosage of the drug contained and the possible method of administration. Tablets can be divided into two main groups depending on whether they are compressed or molded. Compressed tablets are usually produced on a large scale, whereas molded tablets are usually produced on a small scale. Due to the relatively low production capacity of pre-model tablets and the need for dry or sterile conditions during manufacture, this kind of tablet has been gradually replaced by other production methods or dosage forms, so it is rare now.

1.1 Tablet Characteristics

Tablets have many advantages, such as: ①The dose is accurate, the dose and content of the drug in the tablet are in accordance with the prescription, the content difference is small, and the patient takes the dose accurately according to the tablet; the tablet factory can also press the concave groove, which can be divided into two parts. Half or quarter, easy to take smaller doses without losing its accuracy; ②The quality is stable, the tablet will not be damaged or deformed in the general transportation and storage process, so that the drug content will not change for a long time. Tablets are dry solid dosage forms, small in size after compression, light, air, moisture, and dust have a relatively small contact area with them, so the impact on stability is generally relatively small; ③Easy to take, the tablet has no solvent and is small in size, so it is convenient to take , easy to carry; the outside of the tablet is generally clean and beautiful, and the medicine with bad color, taste and smell can be covered by coating; ④ easy to identify, the name and content of the main medicine can be pressed on the tablet, and the tablet can also be dyed with different colors. Color, easy to identify; ⑤ low cost, tablets can be mass-produced by automated machinery, hygienic conditions are easy to control, and packaging costs are low.

However, tablets also have many disadvantages, such as: ①Children and comatose patients are difficult to swallow; ②When improperly prepared and stored, they will gradually deteriorate, so that they are not easy to disintegrate or dissolve in the gastrointestinal tract; ③The storage of tablets containing volatile components is relatively difficult. long-term content decreased.

1.2 Quality Requirements For Tablets

General requirements for good tablets: ① accurate content and small weight difference; ② appropriate hardness and disintegration; ③ uniform color, bright and beautiful; ④ no deterioration within the specified time; ⑤ dissolution rate and bioavailability meet the requirements; ⑥ Comply with hygiene inspection requirements. These requirements include special requirements for specific varieties, which are clearly stipulated in the Pharmacopoeia and Ministry of Drug Standards, so as to ensure the quality of drugs.

Part 2 Tablet Production Technology And Flow

The properties of a tablet are influenced by the formulation and the method of manufacture, and there are great similarities between these two factors. A suitable formulation can make a satisfactory tablet, so it must be designed according to the needs, favorable conditions, method of preparation and equipment used. The main unit operations for tablet preparation are pulverization, sieving, weighing, mixing (solid-solid, solid-liquid), granulation, drying and tabletting, coating and packaging, etc. Its preparation method can be summarized as wet granulation method, dry granulation method and direct compression method, etc. Since the preparation process includes crushing, sieving and tableting, etc., it is necessary to control the temperature and humidity in the production environment. For some products, it must be controlled at a low temperature level, and attention should be paid to cross-contamination between materials during the crushing process.

2.1 Crushing And Sieving

2.1.1 Pulverization

Crushing is mainly the operation process of breaking large solid materials into applicable levels by mechanical force. In the pharmaceutical industry, other methods can also be used to crush solid drugs to the degree of fine powder.

2.1.2 Sieving

①Sieve. After the drug is pulverized, the powder is coarse or fine, and the difference is huge. In order to meet the requirements, the operation process of separating the coarse powder from the fine powder is called sieving, and this mesh tool is called a sieve or a radish.

② Types of drug sieves. Drug sieve refers to the sieve that is uniformly used in the production of pharmaceuticals according to the provisions of the Pharmacopoeia, or standard sieve. In actual production, in addition to some scientific research, industrial sieves are often used. The selection of this type of sieve should be similar to the drug sieve standard without affecting the quality of the drug. The performance and standard of medicine sieve mainly depend on the sieve. According to different sieve making methods, it can be divided into two types: woven sieve and punched sieve. The woven screen is made of copper wire, iron wire, stainless steel wire, nylon wire, and spun silk, and some of them are also woven with horsehair or bamboo wire. When the woven screen is in use, the screen line is easy to shift, so the intersection of the metal screen line is often flattened and fixed. Punching sieve is made by punching out circular or polygonal sieve holes on metal plate. This kind of sieve is durable and the aperture is not easy to change, but the sieve hole should not be very fine. It is mostly used for high-speed crushing and sieving linkage machinery. . Fine powder is generally screened by woven sieve or air separation.

2.2 Ingredients, Mixing

In the tablet production process, the main drug powder and excipients must be mixed several times after being weighed separately according to the prescription to ensure the quality of the tablet. Tablet content differences, disintegration time limit and hardness changes, and content segregation and separation are mostly caused by improper mixing. The main drug powder and excipients are not all mixed uniformly at one time. Firstly, an appropriate amount of diluent is added for dry mixing, and then the curdling agent and wetting agent are added for wet mixing to make a soft and moderate soft material.

2.3 Granulation

Except for some crystalline drugs or powders that can be directly compressed into tablets, generally powdered drugs need to be made into granules before they can be compressed into tablets. This is because:

① There is a certain amount of air in the gap between the powders. When the punch is pressurized, part of the air in the powder cannot escape in time and is pressed into the tablet. In this way, when the pressure is removed, the air inside the tablet expands so that to loosen the tablet;

②The fine powder of some drugs is loose, easy to accumulate, and has poor fluidity, so it cannot flow smoothly from the feed hopper into the die hole, so the impact is more serious, making the content of the tablet inaccurate;

③If there are several kinds of raw and auxiliary material powders in the prescription, the density difference is relatively large. During the tablet pressing process, due to the vibration of the tablet press machine, the heavy ones will sink and the light ones will float up, resulting in stratification, resulting in inaccurate content ;

④The airflow formed during the tableting process tends to cause the fine powder to fly, and the viscous fine powder tends to adhere to the surface of the punch, often causing sticking phenomenon. Therefore, it is necessary to rationally select excipients according to the different properties of the drug, equipment conditions and climate to make granules with a certain thickness and elasticity to overcome.

2.4 Dry

Drying is the process of using thermal energy to remove moisture or other solvents contained in wet solid substances or pastes to obtain dry items. In pharmaceutical production, fresh medicinal materials are dehydrated, raw and auxiliary materials are dehumidified, and drying is used in the preparation of liquids, tablets, granules (infusions), etc.

In an appropriate range, increasing the temperature of the air can increase the temperature of the surface of the material correspondingly, which will speed up the evaporation rate and facilitate drying. However, an appropriate drying temperature should be selected according to the nature of the material to prevent some heat-sensitive components from being destroyed.

The lower the relative humidity of the air, the greater the drying rate. Reducing relative humidity in confined spaces increases drying efficiency. In actual production, hygroscopic agents such as quicklime and silica gel are often used to absorb water vapor in the space, or exhaust and blowing devices are used to update the air flow in the space.

The greater the air flow rate, the faster the drying rate. However, the air flow rate has almost no effect on the deceleration drying stage. This is because increasing the flow rate of the air can reduce the thickness of the air film and reduce the resistance of surface vaporization, thereby increasing the drying rate in the constant-velocity stage. The air velocity has no effect on the internal diffusion, so it has nothing to do with the drying rate in the deceleration stage.

Part 3 Tablet Production Clean Area Division

The tablet workshop can be divided into “control area” and “general production area” according to its process flow. Among them, the “control area” includes production areas such as crushing ingredients, mixing, plate making, pressing, coating, sub-packaging, etc., and other production areas belong to the “general production area”. Double-effect filter for dust removal. According to the requirements of GMP, the cleanliness requirement of the “controlled area” shall not be greater than Class 300,000.