Different manufacturing requirements require varying approaches to tableting.
Tablets remain one of the most widespread and popular dosage forms on the pharmaceutical market. However, although the finished product may look simple and self-contained, the underlying manufacturing processes can be highly complex, involving several state changes as prerequisites to final formulation. At any step in this process, slight miscalculations can result in significant alterations to the bioavailability and stability of the active pharmaceutical ingredient (API).
Almost all tablet manufacturing processes involve granulation; a method of converting small particles of API into agglomerates of greater size and strength. At other stages of the processing pipeline, particles may be reduced, blended, dried, compacted, and coated with other substances. Different types o granulation processes are ideally suited to different types of APIs and end products. Thus, the choice of proper granulation process is critical in ensuring a stable, effective batch of tablets.
This article provides a brief survey of the most common types of granulation processes, along with assessments of their uses and advantages.
Wet granulation offers high efficiency, making it a popular process in tablet manufacturing.
One of the first granulation methods developed was wet granulation, a process of agglomeration in which the powder is “wet massed” with a granulating liquid. This popular method begins by combining the API and excipients into a powder, then combining that powder with a binding solution to form a wet mass. Once this “wet-massing” stage is complete, the moist granules and mixed with disintegrants, glidants and lubricants, and the entire mass is dried.
This wet granulation process offers several benefits over other granulation methods. For example, it enables the powder to be manually or mechanically handled without interfering with the quality of the mix. In addition, wet granulation generates particles of uniform size and sphericity, helping the powder flow more smoothly through the production line.
However, wet granulation can be much more expensive than other granulation methods, due to the intensive time and effort required to process the wet mass. This process also requires significant space, in order to house the large wet-massing equipment. In addition, the mechanical nature o this process raises the likelihood that some material will be lost prior to final drying.
Foam granulation requires less water and binder than wet granulation.
In recent years, pharma developers have aimed to offset the above disadvantages of wet granulation, by engineering a novel process in which binding agents are introduced not in liquid form, but as aqueous foam. In most other aspects, this process is largely identical to wet granulation.
This foam granulation process offers several advantages over traditional wet granulation. The use of foam means less binder and water are required, and the binder can be added at a much more rapid rate, without compromising the stability or potency of the final formulation. Foam granulation also eliminates liquid spray nozzles, preventing the problems of over-wetting and clogged plumbing.
The use of foam granulation also shortens drying time, reducing the overall time necessary to manufacture a batch of tablets. Foam provides more uniform drying conditions that liquid. And perhaps most significantly, the use of foam makes this process ideal for APIs with water sensitivity.
Steam granulation utilizes water vapor to create tablets without modifying bioavailability.
Some pharmaceutical manufacturers go a step beyond foam granulation, and utilize steam as a binder in place of water. This approach yields higher uniformity in powder distribution, while also providing a more rapid rate of diffusion, and a more even balance of heat during the drying stage. Granules manufactured with steam also tend to be more spherical, with a larger surface area than those created via wet-massing. This means the granules can be processed more rapidly, shortening the overall manufacturing time per batch of tablets.
Moreover, the use of sterile water vapor presents no hazard to facility staff, helping create a more OSHA-compliant manufacturing environment. And since steam contains no added chemicals, it can be used to help mask the taste of an unpalatable formulation, without any impact on the stability or bioavailability of the API.
Dry granulation is achieved without heat or solvents, making it useful for sensitive APIs.
If heat and water vapor present too great of a risk to the API, it’s possible to utilize direct mechanical pressure to compress the formulation at room temperature. However, dry granulation is one of the least-used methods of granulation, because it results in tablets that easily break apart into loose powder. If dry granulation is absolutely necessary, it can be achieved via slugging; recompressing the powder and then milling the resulting tablet; or by chilsonation; using a hopper to feed the powder into a compaction zone, where pressure rolls mill them into tablet form.
While direct dry compression is a poor choice of tableting method for most formulations, it can be suitable for dry herbal powders, which retain their efficacy over long periods of storage in cool, dry environments. And if a formulation is to be released immediately upon ingestion, dry granulation may provide an adequate delivery system, without the need for added stabilizers or binding agents.
Thermoplastic granulation eliminates the need to dry tablets.
One viable alternative to dry granulation is thermoplastic granulation, in which a moldable binding agent is added to the formulation. This binder remains in a solid state at room temperature, but has a melting point at slightly higher temperatures. Thus, when the mass is fed through heated compression machinery, the binder melts, forming tablets which then harden as they cool to room temperature.
The selection of a tableting process depends on a number of factors, including the chemical properties of the API as well as the desired mechanical features of the finished tablets. While heat-based granulation techniques are unsuitable for APIs with temperature sensitivities, and liquid- or foam-based processes may be harmful to water-sensitive APIs, these methods can provide many of the benefits of dry granulation, without the fragility of a dry-compressed tablet product. These advantages make foam and steam granulation highly useful for inert APIs that must be manufactured at low cost.
