Types Of Wet Granulation

Wet granulation is gaining importance due to the recent progress that has made it easy for pharmacists to adopt those techniques with minimum limitations. Several advance techniques have been provided to the pharmaceutical industry including

1.Steam Granulation

The main difference in steam granulation in comparison to conventional wet granulation method is the usage of steam as a binder instead of water as granulating fluid. Usually a steam generator and a mixer (high shear) is sufficient for the steam granulation method.

Rotary Drum for Steam Granulation

Benefits

• The advantage of steam is that it can diffuse better readily into the powder due to its purity and gaseous state which also helps in better drying.
• Produces spherical granules with more surface area less processing time

Limitations

• This method cannot be used for thermolabile drugs due to high temperature of steam which can affect the properties of the drug.
• High energy required for making steam
• This technique generates granules with high dissolution rate compared to conventional wet granulation techniques.

Application

This method is being employed greatly in the pharmaceutical industry as it is ecofriendly due to no involvement of organic solvents.

2.Moisture Activated Dry Granulation

MADG or Moisture activated dry granulation is modification of the classical wet granulation technique. It is done in two main steps first by wet agglomeration which is done by addition of small quantity of water to the mixture of drug and binder. The second step after agglomeration is drying which is done by addition of silicon dioxide or microcrystalline cellulose absorbing the extra moistness.

The name moisture activated dry granulation usually creates confusion as someone can get dry granulation to be involving compactors and slugging techniques but actually the drying process in MADG is quite different and does not involve any of the two.

Pharmaceutical Granulation Plant

Benefits

Main advantages of this technique are

• Less chances of lump formation due to less water required for the process
• less energy requirement,
• Efficient
• widely applicable.

Limitations

Accounting to the stability and processing issues this technique cannot work best for

• moisture sensitive drugs
• hygroscopic drugs

Application

This technique is getting popular in the pharmaceutical industry and is being widely used due to its efficiency and less water requirement.

3.Thermal Adhesion Granulation or TAG

This advanced technique of wet granulation involves both water and solvent for granulation and as the name suggests it also utilizes heat to expedite the granulation process. The drug along with the excipient is heated at a high temperature and less amount of liquid is used which eliminates the requirement of the drying process.

Binders are a very important element in wet granulation without them it's impossible to achieve specific properties of the granules. A good binder is responsible for required adhesive and cohesive forces between surfaces of different particles and ensures the binding ability.

The significance of binder in wet granulation makes the selection process much critical as much of the properties of resulting granules are dependent upon it.

Benefits

• This technique is useful for generating particles with high tensile strength and better flow properties.
• No need for an additional drying process
• Simple and convenient

Limitations

• It cannot be used for all types of binders and drugs that are heat-sensitive.
• Special equipment for heat generation is required
• High energy inputs are needed.

Application

This technique is a good alternative to conventional wet granulation techniques and is adopted by the pharmaceutical industries as it is simple and fewer steps are involved.

4.Melt granulation

Also known as thermoplastic granulation involves the usage of binders that have low melting temperatures i.e. 50-90 °C). the binders are added during the granulation process in two ways, as solid particles or as a molten liquid and then the drug, binder, and excipients mixture is heated to a suitable temperature according to the binder’s melting temperature.

Benefits

• This technique can be used as an alternative to other wet granulation techniques that are not suitable for moisture-sensitive drugs.
• It eliminates the usage of water which ultimately eradicates the requirement of drying after agglomeration.

Limitation

• Similar to most heat involving wet granulation techniques, this technique is not best for heat-sensitive drugs.

Application

Pharmaceutical industries have shown interest in this method owing to the advantages over wet granulation techniques for the preparation of drug formulations. Also, as it eliminates the environmental concerns due to the elimination of organic solvents it is becoming popular.

5.Foam granulation

Foam granulation is similar to spray agglomeration, but the binder is poured in form of foam onto the powder instead of spraying. This technique is a patent of Dow Chemical Company, Midland, MI. A foam generator is used in the binder tank to convert the binder into foam form which is then introduced onto the powder. This technique provides uniform distribution of the binder to the powder.

Benefits

• The processing time is less as it requires less binding liquid thus the drying process is shorter making it faster.
• This wet granulation technique is useful for water-sensitive formulations.
• In a shorter time, more binder mass is absorbed via foam granulation as compared to the addition of liquid or spray thus making 40% larger nuclei.
• Uniformity of granules is achieved
• Controlled and immediate release of drug

Limitations

• Foam generation requires high energy and resource as compared to other techniques.

Application

This technology is gaining importance in the pharmaceutical industry and being employed by many companies due to its various advantages the most beneficial being even distribution of drugs. 

6.Freeze Granulation

Freeze granulation is based on two primary steps. The powder suspension is sprayed on liquid nitrogen which results in instant freezing of the droplets into granules which are dried in the subsequent step via sublimation. Both water-based and solvent-based granules can be synthesized by this method.

Freeze Granulation of Particles

Benefits

• Homogenous particles are formed by this technique.
• Freeze drying or low temperature minimizes damage and enhances the stability of the drug.
• Controlled granule density
• Less material gets wasted

Limitations

Mostly water is preferred over organic solvents in this process which is the limitation of the technique because of less solubility of drugs and excipients.

Application

Freeze granulation is a widely used technique in the pharmaceutical as well as ceramic and food industries.

7.Reverse wet granulation

It is the recent development in wet granulation technique where the dry powder is immersed into the solvent or binder which is then broken down into granules under controlled conditions. First, the binder solvent is prepared, and the dry excipients are mixed with it in a granulator. Granule formation occurs when other dry excipients are added to the drug-binder mixture. The wet granules undergo milling after drying in the subsequent steps.

Reverse Granulation

Benefits

• This method produces granules having good flow and handling properties.
• The best characteristic is uniform dissolution in comparison with other wet granulation techniques.
• Controlled breakage of the granules occurs in this process resulting in tablets having an even dissolution rate

Limitation

• The granules generated by this process are often with less intragranular porosity and of greater mass mean diameter.

Application

• This technique can be used for fewer water-soluble drugs due to the close contact of between the drug and polymer.