The Basics of Wet Granulation
March 13, 2023

1. Reasons of equipment manufacturing

Wet granulation: Add binder or wetting agent to the raw material powder to make soft material, sieve to make wet granules, dry the wet granules and then sizing. The granules made by wet granulation have the advantages of good surface modification, beautiful appearance, strong wear resistance and good compression formability.

The principle of wet granulator: firstly, the liquid in the binder wets the surface of the drug powder to generate adhesion between the powder particles, and then under the action of liquid bridging and external mechanical force, it is made into particles of a certain shape and size. After drying, it finally consolidates in the form of a solid bridge.

Wet granulation mainly includes the process of making soft material, making wet granules, drying wet granules and sizing.


2. Making soft material

Mix the fine powder of raw and auxiliary materials prepared according to the prescription (about three minutes), add an appropriate amount of wetting agent or adhesive and mix well to form a soft material.

Selection principle of wetting agent or adhesive:

(1)Fine powder, loose texture, poor dryness and viscosity, low solubility in water: choose a more viscous adhesive, and the amount of adhesive should be more.
(2)The solubility in water is high, and the viscosity of the raw and auxiliary materials is strong: choose a wetting agent or a less viscous adhesive, and the amount of the adhesive should be relatively small.
(3)Sensitive to moisture, easy to hydrolyze: Do not choose water as the solvent of the adhesive, choose absolute ethanol or other organic solvents as the solvent of the adhesive
(4)Sensitive to heat and easy to decompose: try not to use water as the solvent of the adhesive, and use ethanol with a certain solubility as the solvent of the adhesive to reduce the drying time and temperature of the particles
(5)Stable against humidity and heat: water with low cost is selected as the solvent of the adhesive.

Issues that should be paid attention to when making soft materials:

(1) The type and amount of adhesive should be determined according to the nature of the material;
(2) The concentration and stirring time of the adhesive should be flexibly controlled according to different varieties;
(3) Soft material quality. Due to the differences in raw and auxiliary materials, it is difficult to set a unified standard. Generally, it is mastered by experience. It can form agglomerates when squeezed tightly with hands, and can be broken apart with light pressure with fingers.
(4) When making soft materials, the stirring and cutting time should be properly controlled. Generally, it can be mastered by experience. It can form agglomerates without sticking to hands when squeezed tightly by hand, and it can be separated by light pressure with fingers. If the mixing time is long, the viscosity is too strong and granulation is difficult; if the mixing time is short, the viscosity is not strong and the granulation is not good.

3. Making wet granules

Make soft material pass through 14 mesh or 16 mesh screen to make granules.
Problems that should be paid attention to when making wet granules:
(1)If the particles fall from the sieve and form long strips, it indicates that the soft material is too wet, and there are too many wetting agents. On the contrary, if the soft material is powdery after passing through the sieve, it indicates that the soft material is too dry and should be adjusted appropriately.
(2)If the sieve is loosely installed during granulation, the viscosity of the soft material can be increased when the drum is reciprocatingly rotated to stir and knead, and the obtained wet granules are thick and tight. On the contrary, the obtained particles are fine and loose. Therefore, the tightness of the screen installed in production should be moderate.

Commonly used equipment: swing granulator; screen: stainless steel screen


4. Drying wet granules

The wet granules obtained by sieving should be dried immediately to avoid agglomeration or compression deformation.
Drying temperature: depends on the nature of raw materials, generally 50-60°C; for some drugs that are stable to humidity and heat, the drying temperature can be appropriately increased to 80-100°C.
Dryness: Control by measuring the moisture content, and retain appropriate moisture according to the difference of each specific variety, generally about 3%.

Drying Equipment

Circulation oven: set multi-layer brackets in the dryer, place stainless steel plates on the brackets, the air is heated by the preheater and enters the drying room, and passes through the surface of the material in a horizontal direction for drying. (Stainless steel plates can be used to spread out the prepared wet granules and turn them from time to time to solve the problem of agglomeration and deformation of wet granules.)
Features: The equipment is simple and adaptable, but the labor intensity is high, the drying speed is slow, and the heat consumption is large.
Boiling granulator: hot air passes through the loose granular or powder material layer from bottom to top to form a fluidized state for drying, also called boiling dryer.
Features: Simple structure, convenient operation, intense relative movement between particles and hot air flow, large contact area, and fast drying speed.

5. Sizing

After the wet granules are dried, they need to be screened and sized to break up the agglomerated granules, so as to meet the tablet compression requirements.
Blank granulation method: For drugs that are unstable to humidity and heat and have a small dose, auxiliary granules and other drugs that are stable to humidity and heat can be granulated by wet method first, and after drying and granulation, the drugs that are not resistant to humidity and heat can be combined with the granules. The method of making auxiliary granules into dry granules, and then mixing the drug with the granules (compression or subpackaging) is called blank granulation method.
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