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 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.
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.