Direct compression is the most advanced technology. It involves only blending and compression. Thus offering advantage particularly in terms of speedy production. Because it requires fewer unit operations, less machinery, reduced number of personnel and considerably less processing time along with increased product stability.
1. Assignment
Course-Advanced Pharmaceutical Technology
Course Code-PHR 5021.1
Topic –Direct Compression Method
Prepared For:
Dr. Md. Selim Reza
Professor,
Department of Pharmaceutical Sciences,
North South University.
Prepared By:
Md. Mominul Islam
ID# 162 1405 673
NSU_Mpharm-Summer, 2017.
2. Tablet ManufacturingMethods
Direct compression
Introduction
In early days, most of the tablets require granulation of the powdered Active Pharmaceutical
Ingredient (API) and Excipients. At the availability of new excipients or modified form of old
excipients and the invention of new tablet machinery or modification of old tablet machinery
provides an ease in manufacturing of tablets by simple procedure of 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.
3. 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.
Amongst the techniques used to prepare tablets, direct compression is the most advanced
technology. It involves only blending and compression. Thus offering advantage particularly in
terms of speedy production. Because it requires fewer unit operations, less machinery, reduced
number of personnel and considerably less processing time along with increased product
stability.
By definition , direct compression are as follows…
The term “direct compression” is defined as the process by which tablets are compressed directly
from powder mixture of API and suitable excipients. No pretreatment of the powder blend by
wet or dry granulation procedure is required.
On the Otherhand, Direct compression is a dry process where in the powdered material (tablet
formulation) is compressed directly into the tablets without the physical nature of the former
being modified.
Example-
1.Formulation of Ascorbic Acid Tablets.
2.Formulation of Chewable Antacid Tablets.
The events that motivates the industry people to use direct compression
technique:
4. I.Commercial availability of the directly compressible excipients possessing both good
compressibility and good flowability.For example, Spray dried lactose, Anhydrous lactose,
Starch-1500, microcrystalline cellulose, Di-Pac, Sorbitol
II. Major advances in tablet compression machinery,
i) Improved positive die feeding
ii) Precompression of powder blend
Manufacturing steps:
Direct compression involves comparatively few steps:
i)Milling of drug and excipients.
ii)Mixing of drug and excipients.
iii)Tablet compression.
5. Advantages of Direct Compression
Direct compression is more efficient and economical process as compared to other
processes, because it involves only dry blending and compaction of API and necessary
excipients.
The most important advantage of direct compression is economical process.Reduced
processing time, reduced labor costs, fewer manufacturing steps, and less number of
equipments are required, less process validation, reduced consumption of power.
Elimination of heat and moisture, thus increasing not only the stability but also the
suitability of the process for thermolabile and moisture sensitive API’s.
Particle size uniformity.
Prime particle dissolution.
In case of directly compressed tablets after disintegration, each primary drug particle is
liberated. While in the case of tablets prepared by compression of granules, small drug
particles with a larger surface area adhere together into larger agglomerates; thus
decreasing the surface area available for dissolution.
The chances of batch-to-batch variation are negligible, because the unit operations
required for manufacturing processes is fewer.
Chemical stability problems for API and excipient would be avoided.
Provides stability against the effect of aging which affects the dissolution rates.
Merits over wet granulation process
The variables faced in the processing of the granules can lead to significant tableting
problems.
Properties of granules formed can be affected by viscosity of granulating solution, the
rate of addition of granulating solution, type of mixer used and duration of mixing,
method and rate of dry and wet blending.
The above variables can change the density and the particle size of the resulting granules
and may have a major influence on fill weight and compaction qualities.
6. Drying can lead to unblending as soluble API migrates to the surface of the drying
granules.
Disadvantages of Direct Compression
Excipient Related
i)Problems in the uniform distribution of low dose drugs.
ii)High dose drugs having high bulk volume, poor compressibility and poor flowability are not
suitable for direct compression. For example, Aluminium Hydroxide, Magnesium Hydroxide
iii)The choice of excipients for direct compression is extremely critical. Direct compression
diluents and binders must possess both good compressibility and good flowability.
iv)Many active ingredients are not compressible either in crystalline or amorphous forms.
v)Direct compression blends may lead to unblending because of difference in particle size or
density of drug and excipients. Similarly the lack of moisture may give rise to static charges,
which may lead to unblending.
vi)Non-uniform distribution of colour, especially in tablets of deep colours.
Process Related
i)Capping, lamination, splitting, or layering of tablets is sometimes related to air entrapment
during direct compression. When air is trapped, the resulting tablets expand when the pressure of
tablet is released, resulting in splits or layers in the tablet.
ii)In some cases require greater sophistication in blending and compression equipments.
iii)Direct compression equipments are expensive.
7. Direct compression Excipients
Direct compression excipients mainly include diluents, binders and disintegrants. Generally these
are common materials that have been modified during the chemical manufacturing process, in
such a way to improve compressibility and flowability of the material. The physicochemical
properties of the ingredients such as particle size, flowability and moisture are critical in direct
compression tableting. The success of direct compression formulation is highly dependent on
functional behavior of excipients.
An ideal direct compression excipient should possess the following attributes
i) It should have good compressibility.
ii) It should possess good hardness after compression, that is material should not possess any
deformational properties; otherwise this may lead to capping and lamination of tablets.
iii) It should have good flowability.
iv) It should be physiologically inert.
v) It should be compatible with wide range of API.
vi) It should be stable to various environmental conditions (air, moisture, heat, etc.).
vii) It should not show any physical or chemical change in its properties on aging.
viii) It should have high dilution potential. i.e. Able to incorporate high amount of API.
ix) It should be colourless, odorless and tasteless.
x) It should accept colourants uniformity.
xi) It should possess suitable organoleptic properties according to formulation type, that is in
case of chewable tablet diluent should have suitable taste and flavor. For example mannitol
produces cooling sensation in mouth and also sweet test.
xii) It should not interfere with bioavailability and biological activity of active ingredients.
8. xiii) It should be easily available and economical in cost.
Major excipients required in direct compression
I.Diluents
II.Binders
III.Disintegrants
Diluents
Selection of direct compression diluent is extremely critical, because the success or failure of
direct compression formulation completely depends on characteristics of diluents. There are
number of factors playing key role in selection of optimum diluent. Factors like- Primary
properties of API (particle size and shape, bulk density, solubility), the characteristics needed for
processing (flowability, compressibity), and factors affecting stability (moisture, light, and other
environmental factors), economical approach and availability of material. After all, one can say
that raw material specifications should be framed in such a way that they provide an ease in
manufacturing procedures and reduce chances of batch to batch variation.
Binders
Binders are the agents used to impart cohesive qualities to the powdered material. The quality of
binder used has considerable influence on the characteristic of the direct compression tablets.
The direct compression method for preparing tablets requires materials which are not only free
flowing but also sufficiently cohesive to act as binder.
9. Conclusion:
Today, direct compression plays a key role in the pharmaceutical industry as the continuing trend
towards generics requires manufacturers to design their production processes as efficient as
possible. This is what direct compression delivers – formulation components are homogenized
by mixing and then directly compressed into the final dosage form.
However, in order to achieve a robust and lasting dosage form, the to be compressed functional
components used in the mix must exhibit good flowability and compressibility. And this factor
gets more important in case
the amount of functional excipient in the formulation is reduced, i.e. due to a required high
drug load or
the drug itself is very poorly flowable or compressible.
This is why we offer a range of high to highly effective direct compression binders, disintegrants
and lubricants that will provide you all the design space you need for your formulation.
And if you are working on a project where time-to-market is absolutely critical, we offer
specialized ready-to-use premixes for tablets, orally disintegrating tablets and other dosage forms
that will enable you to take the fast track towards your direct compression process.