Dear Jayanth,

Tablets can be made by two different methods:

1-Direct compaction

or 2-via dry or wet granulation

Direct Compression Versus Granulation

 Mar 07, 2011

By Liesbeth Meeus

Pharmaceutical Technology Europe

Volume 23, Issue 3

Compressed tablets are the most widely used solid dosage form so they must satisfy a number of physical requirements in terms of hardness, disintegration ability, friability and uniformity. To provide these tablet characteristics in accordance with the chosen ingredients, manufacturers can use three different processing technologies: direct compression, dry granulation and wet granulation.

Direct compression

Direct compression is a popular choice because it provides the shortest, most effective and least complex way to produce tablets. The manufacturer can blend an API with the excipient and the lubricant, followed by compression, which makes the product easy to process. No additional processing steps are required.

 Moisture or heatsensitive ingredients, which would be contraindicated in wet granulation, can also be used in this type of process. However, it does require a very critical selection of excipients in comparison to granulation processes because the raw materials must demonstrate good flowability and compressibility for successful operation. 

Both high and low doses of API present a challenge in this respect. Most APIs tend to have poor compressibility, which affects the quality of tablets if the formulation calls for a large proportion of API. At the same time, there can also be problems when low amounts of actives need to be incorporated into tablets because it is difficult to accurately blend a small amount of active in a large amount of excipient to achieve the desired uniformity and homogeneity.

For instance, segregation of the different components can occur. This means there is not a uniform distribution of tablet ingredients being fed to the press, and thus batchtobatch consistency of the manufactured tablet cannot be assured.

One of the principal risk factors for segregation is the wide particle size distribution in direct compression formulations, in which active ingredients tend to be at the fine end of the range. Where there is a wide range of particle sizes, there is an increased likelihood of sifting, where the smaller particles 'slip through' the bigger ones.

Other bulk powder properties are also important for successful tabletting, such as good flowability, and all of these factors combine to place a high requirement on the excipients used for direct compression.

2-via wet or dry granulation.

Powder blending

The successful mixing of powder is more difficult than mixing liquid, as perfect homogeneity is difficult to achieve. A further problem is the inherent cohesiveness and resistance to movement between the individual particles. The process is further complicated in many systems by the presence of substantial segregation influencing the powder mix. This arises from the difference in size, shape, and density of the component particles. The powder/granules blending are involved at stage of pre granulation and/or post granulation stage of tablet manufacturing. Each process of mixing has an optimum mixing time, and longer mixing may result in an undesired product. The optimum mixing time and mixing speed must be evaluated. Blending prior to compression is normally achieved in a simple tumble blender. The blender may be a fixed blender into which the powders are charged, blended and discharged. It is now common to use a bin blender. In special cases of mixing a lubricant, over mixing should be particularly monitored. The various blenders used include "V" blender, Oblicone blender, Container blender, Tumbling blender, Agitated powder blender. But nowadays to optimize the manufacturing process particularly in wet granulation the various improved equipment which combines several processing steps (mixing, granulation and/or drying) are used. They are the "Mixer granulator" and "High shear mixing machine".

Granulation

If a powder blend's properties do not suit direct compression tabletting, manufacturers will turn to granulation processes to create the desired flowability and low dustability. These characteristics are required to minimise tablet weight variations, and ensure high density for high tablet filling weight and high moldability for hard tablet manufacture.

Granulation narrows the particle size distribution of a tablet formulation's bulk powder, eliminating segregation problems. This in turn ensures superior compressibility in the tabletting process, permitting higher quantities of API to be used and ensuring good active distribution in the tablet. However, granulation is a more time-consuming technique compared with direct compression and there is also a risk of product cross-contamination and product loss during the different processing steps (granulation, drying, sieving). All of these factors can increase costs compared with direct compression.

Dry granulation is more flexible than direct compression. Compared with wet granulation, however, it has a shorter, more cost-effective manufacturing process. Because it does not entail heat or moisture, dry granulation is especially suitable for active ingredients that are sensitive to solvents, or labile to moisture and elevated temperatures

Tablet compression

After the preparation of granules (in case of wet granulation) or sized slugs (in case of dry granulation) or mixing of ingredients (in case of direct compression), they are compressed to get final product. The compression is done either by single punch machine (stamping press) or by multi station machine (rotary press). The tablet press is a high-speed mechanical device. It 'squeezes' the ingredients into the required tablet shape with extreme precision. It can make the tablet in many shapes, although they are usually round or oval. Also, it can press the name of the manufacturer or the product into the top of the tablet.

Each tablet is made by pressing the granules inside a die, made up of hardened steel. The die is a disc shape with a hole cut through its centre. The powder is compressed in the centre of the die by two hardened steel punches that fit into the top and bottom of the die. The punches and dies are fixed to a turret that spins round. As it spins, the punches are driven together by two fixed cams - an upper cam and lower cam. The top of the upper punch (the punch head) sits on the upper cam edge .The bottom of the lower punch sits on the lower cam edge.

The shapes of the two cams determine the sequence of movements of the two punches. This sequence is repeated over and over because the turret is spinning round. The force exerted on the ingredients in the dies is very carefully controlled. This ensures that each tablet is perfectly formed. Because of the high speeds, they need very sophisticated lubrication systems. The lubricating oil is recycled and filtered to ensure a continuous supply. Common stages occurring during compression

Stage 1: Top punch is withdrawn from the die by the upper cam Bottom punch is low in the die so powder falls in through the hole and fills the die

Stage 2: Bottom punch moves up to adjust the powder weight-it raises and expels some powder

Stage 3: Top punch is driven into the die by upper cam Bottom punch is raised by lower cam Both punch heads pass between heavy rollers to compress the powder

Stage 4: Top punch is withdrawn by the upper cam Lower punch is pushed up and expels the tablet is removed from the die surface by surface plate

Stage 5: Return to stage 1

Tablets can be made by two different types of tabletting machines:

1-Single punch

2-Rotary press machine

Tablet press

From Wikipedia, the free encyclopedia

 A tablet press in operation

A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A press can be used to manufacture tablets of a wide variety of materials, including pharmaceuticals, illicit drugs such as MDMA, cleaning products, and cosmetics. To form a tablet, the granulated material must be metered into a cavity formed by two punches and a die, and then the punches must be pressed together with great force to fuse the material together.[1]

A tablet is formed by the combined pressing action of two punches and a die. In the first step of a typical operation, the bottom punch is lowered in the die creating a cavity into which the granulated feedstock is fed. The exact depth of the lower punch can be precisely controlled to meter the amount of powder that fills the cavity. The excess is scraped from the top of the die, and the lower punch is drawn down and temporarily covered to prevent spillage. Then, the upper punch is brought down into contact with the powder as the cover is removed. The force of compression is delivered by high pressure compression rolls which fuse the granulated material together into a hard tablet. After compression, the lower punch is raised to eject the tablet.[2]

 An old rotary tablet press

There are 2 types of tablet presses: single-punch and rotary tablet presses. Most high speed tablet presses take the form of a rotating turret that holds any number of punches. As they rotate around the turret, the punches come into contact with cams which control the punch's vertical position. Punches and dies are usually custom made for each application, and can be made in a wide variety of sizes, shapes, and can be customized with manufacturer codes and scoring lines to make tablets easier to break. Depending on tablet size, shape, material, and press configuration, a typical modern press can produce from 250,000 to over 1,000,000 tablets an hour. [3]

https://en.wikipedia.org/wiki/Tablet_press

Hoping this will be helpful,

Rafik

Knowledge gap areas includes:

1. Excipients compatibility

2. Novel Drug Delivery System

3.Targeted drug delivery

4.Tabletting problems and solutions

5. Proper use of Excipients and polymers