Ideal Granule Size Distribution Based on Tablet Weight
In pharmaceutical tablet manufacturing granule size plays a critical role in ensuring smooth processing, uniformity, flowability, and compressibility. The optimal granule size depends on multiple factors, including the tablet weight, dosage form type, API properties, and manufacturing method. While there is no strict one-size-fits-all rule, certain guidelines are generally followed based on tablet weight ranges.
For low-weight tablets, typically those weighing less than 100 mg, finer granules are usually preferred. These is within the 40 to 60 mesh range, which corresponds to granules sized between approximately 250 to 420 microns (0.25–0.42 mm). Finer granules are needed in these cases to ensure uniform distribution of the active ingredient, especially when the dose is low and content uniformity is critical. However, care must be taken to avoid excessively fine particles that may lead to poor flow, dusting, and sticking during compression.
For tablets in the 100–300 mg range, granules of moderate size are typically used, usually in the 25 to 40 mesh range, corresponding to 420–710 microns. These granules strike a good balance between flowability and compressibility, making them ideal for general-purpose formulations. The particle size is large enough to flow well into the dies but still small enough to compress uniformly without trapping air or causing capping or lamination.
As the tablet weight increases to the 300–600 mg range, slightly coarser granules may be used, often within the 18 to 25 mesh range (about 710 microns to 1 mm). These larger granules help facilitate efficient die filling, especially on high-speed rotary tablet presses, and reduce problems like bridging or flow interruption. They also tend to compress well, particularly when combined with plastically deforming excipients or binders.
For large tablets weighing more than 600 mg, such as effervescent tablets or high-dose actives like metformin or paracetamol, granule sizes in the 16 to 20 mesh range may be used. The coarser granules in these cases are preferred to ensure excellent flow and faster die filling, which is critical in maintaining weight uniformity during compression. However, compressibility must be closely monitored, as larger granules may reduce bonding surface area.
In all cases, a narrow and uniform granule size distribution is ideal. Excessive fines can lead to sticking, poor flow, and segregation, while overly coarse or variable sizes can result in weight variation, poor hardness, and friability issues. So, the granulation process—whether wet or dry—should be optimized to achieve the desired particle size profile for the given formulation.
It’s also important to note that for DC processes, both the API and excipient particle sizes matter. Most excipients used in DC are designed to have controlled particle sizes around 100 to 300 microns to ensure good flow and compressibility without requiring further granulation.
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Resource Person: Moinuddin Syed. Ph.D, PMP®
