Manufacture Of Pharmaceutical Tablet By Direct Compression

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

Granulating machine

Direct compression formulations can be developed with minimal numbers of excipients. Typically the minimum excipients needed are a diluent (filler binder), a disintegrant and a lubricant. Additional components may include a glidant, a surfactant, pigments and stabilising agents.

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. Moisture or heat sensitive ingredients, which would be contraindicated in wet granulation, can also be used in this type of process.

Read Also: Manufacture of pharmaceutical tablet method

Ideal Properties Of Excipients For Direct Compression

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 a 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 a 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 a cooling sensation in the mouth and also a sweet taste

xii) It should not interfere with bioavailability and biological activity of active ingredients

xiii) It should be easily available and economical in cost

Application Of Direct Compression

Among several requirements, the compression mix has to flow to ensure a consistent tablet weight; it has to compress and compact into robust tablets; and the resulting tablets have to remain stable over time to maintain safety and efficacy.

Three key factors for successful tableting are flow and compactability of the compression mix, and drug content uniformity in the mix and the final tablets. All of these factors are likely to be affected by drug dose.

The most obvious factor in determining whether DC is applicable to a certain drug substance is dose.

Read Also: Manufacture of pharmaceutical tablet by granulation method

For low dose drugs, flow and compaction of the compression mix are largely conferred by the excipients and the primary concern is likely to be achievement of good content uniformity in the blend and in the tablets. For medium dose drugs flow of the compression mix may become a critical factor, and for high dose drugs the flow and compaction are highly dependent on the properties of the drug substance.

Low dose is taken to mean 10 mg or below, medium dose is taken to mean 10 mg to 50 mg and high dose is taken to mean above 50 mg

Formulation And Process Considerations

1.

API dose and final tablet size

2. API particle size and compressibility

3. Binder and diluent particle size and bulk density

4. Powder blend adhesive and cohesive characteristics

5. Powder blend moisture content

6. Powder blend flow and compressibility

7. Type of lubricant and lubrication time

8. Manufacturing train design and segregation potentials

Direct Compression Process

The manufacture of tablets by direct compression involves comparatively few steps and they include:

1. Premilling of formulation ingredients (active drug substance and excipients) by weighing, grind and sieve

2. Homogeneous mixing of the active ingredients and excipients

3. Compression of the mixed powders into tablets

Read Also: Manufacture of pharmaceutical tablet by wet granulation method

Advantage Of Direct Compression

1. Cost Effectiveness

The prime advantage of direct compression over wet granulation is economic since the direct compression requires fewer unit operations. This means less equipment, lower power consumption, less space, less time and less labor leading to reduced production cost of tablets. 

2. Stability

Direct compression is more suitable for moisture and heat sensitive APIs, since it eliminates wetting and drying steps and increases the stability of active ingredients by reducing detrimental effects. Changes in dissolution profiles are less likely to occur in tablets made by direct compression on storage than in those made from granulations. This is extremely important because the official compendium now requires dissolution specifications in most solid dosage forms. 

3. Faster Dissolution

Disintegration or dissolution is the rate limiting step in absorption in the case of tablets of poorly soluble API prepared by wet granulation. The tablets prepared by direct compression disintegrate into API particles instead of granules that directly come into contact with dissolution fluid and exhibit comparatively faster dissolution. 

4. Less Wear And Tear Of Punches

The high compaction pressure involved in the production of tablets by slugging or roller compaction can be avoided by adopting direct compression. The chances of wear and tear of punches and dies are less. 

5. Simplified Validation

Materials are "in process" for a shorter period of time, resulting in less chance for contamination or cross contamination, and making it easier to meet the requirement of current good manufacturing practices. Due to fewer unit operations, the validation and documentation requirements are reduced. Due to the absence of water in granulation, chance of microbial growth is minimal in tablets prepared by direct compression.

Disadvantage Of Direct Compression

1. 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.

Read Also: Manufacture of pharmaceutical tablet by dry granulation

2. 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.

3. Direct compression excipients are often more expensive than other tablet excipients used in wet granulation or slugging.

4. 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 batch to batch consistency of the manufactured tablet cannot be assured.

5. Tablet defects such as sticking, capping and lamination are usually pronounced in tablets manufactured by direct compression method.