A Comparative Analysis of Granulation & Direct Compression Method

When we think of medicines, the very first image that pops into the mind is that of a hardened solidified structure, commonly known as a tablet or a pill, which can cure ailments but is terrible to the taste.Given the disdain that patients carry for medicine, it is not surprising that very few of us take an interest in the background machinations that go into creating those tiny pellets.

To be able to create a homogenous mixture that has the precise amount of the powdered API (Active Pharmaceutical Ingredient), which isn’t usually required in large doses, the tablet should be chiefly composed of an inert carrier (an excipient, also in powder form). This inert carrier not only gives uniformity and structure to the final product but also facilitates fluid delivery of the medication when administered. This can be a single excipient or a combination of excipients, each being introduced for a separate specific function.

This limitation means that drug manufacturers must be precise and efficient. They are hard-pressed to find a method that involves faster processing times as well as a high-grade end product with precision dosing. Of late, the pharma industry deploys two different processes in their creation:

Granulation & Direct Compression

1. Granulation, which can be further sub-categorized into:

• Dry Granulation

This method involves mechanical compression of smaller molecules to create an agglomerated macro particle (called Granule), large enough to be administered in a dosage form.

• Wet Granulation

This method involves a liquid solvent as the medium for granulation rather than mechanical compression. It has the advantage of reducing powder contamination when compared with the dry method.

2. Direct Compression

• Using Induced Die feeders
• Using Dry Binders
• Using other excipients

Historically speaking, granulation has always been the industry standard in tablet manufacturing given that the process has multiple benefits like:

1. Maintaining the mix quality.
2. Better flow control.
3. Uniformity of the API density.
4. Lesser chances of air entrapment in the product molecule.
5. Greater control over the quantity of dosage, thus helping in creating high or low dosage medication as well as anything in between.

Comparing with this, Direct compression comes with a plethora of benefits, specifically from the point of view of manufacturing in the sense that:

1. It has fewer process steps, leading to a minimalistic requirement for equipment, thereby being highly cost-effective.
2. Highly stable product since the heat due to dry granulation or involvement of a solvent as in wet granulation are both avoided.
3. The dissolution characteristics of excipients are unhindered as the excipients chosen for this process are always of a high binding capacity.
4. Avoids contamination of the product or the equipment since the mixing and lubrication excipients can usually be a single compound or both processes can be carried in the same step.

However, one cannot ignore certain glaring issues that might occur with this tableting process:

1. Both high-dose and low-dose products are hard to create as there is lesser control over the blending of the excipients and the API with the fewer number of steps.
2. The majority of drugs aren’t compatible with this process simply due to not having enough compressibility.
3. The choice of excipients used is highly limited as most chemicals do not possess the properties for an ideal excipient product for most APIs.

Conclusion

Following the above discussions, it can be concluded that even though Direct Compression is a cheaper and more cost-effective method, it is relatively new and yet to be made a universal process that can handle at least a majority of the commonly tableted drugs, if not all. No wonder then, that Granulation is the current favorite of the drug industry, which not only needs to consider cost but also the quality of the product being manufactured, and the applicability of the method being used for the creation.

About ZIM Laboratories

ZIM Labs is an innovative drug delivery solution provider focusing on improving patient convenience and adherence to drug intake. We offer a range of technology-based drug delivery solutions and non-infringing proprietary manufacturing processes for the production and supply of innovative and differentiated generic pharmaceutical products to our customers globally. At ZIM Labs we provide our customers a comprehensive range of value-added solid dosage differentiated generic products in semi-finished and finished categories/formulations. These include granules, pellets (sustained, modified, extended-release), taste-masked powders, suspensions, tablets, capsules, and recently developed Oral Thin Films (OTF).