In pharmaceutical formulation development, the bulk/tapped density and particle size of the active ingredient are crucial in determining the success of the granulation process. The choice of granulator type also plays a pivotal role in determining the final characteristics of the granules, which directly affect tablet quality.
Here are some key factors to consider in granulation design:
1. Granulator Type & its Impact on Granule Quality
The granulator type used in the process significantly influences the characteristics of the final product. High shear granulators (such as the Diosna™ type) are ideal for producing high-density granules with improved flow properties. On the other hand, fluidized bed granulators tend to produce moderate density granules, which may not provide the desired flow or compressibility properties for tablets. In particular, poorly flowing and coarse actives often require high shear granulation to improve flow and uniformity.
2. Extra- vs. Intra-Granular Excipients Placement
The placement of excipients like microcrystalline cellulose (MCC), disintegrants, and starch in the granulation blend can have a significant impact on the granule formation and flow properties. Adding excipients extra- or intra-granularly plays an important role in fine-tuning dissolution profiles. For instance, adding disintegrants intra-granularly can improve dissolution speed and granule strength, whereas extra-granular additions are typically used to enhance disintegration in the final tablet.
3. Lubricant Addition Timing
It’s important to ensure that the unlubricated granule blend is fully homogeneous before adding the lubricant. If the lubricant is added too early, it can hinder the flow properties of the granules. The proper method is to mix the excipient blend first, followed by the lubricant to enhance tablet ejection from the die and maintain good flow properties. Excessive lubricant blending after the addition can impact the tablet's dissolution rate and overall quality.
4. High-Dose Active Ingredients
When the active dose of a tablet is large, typically between 750–850 mg, there are challenges in converting the active ingredient into a direct compressible form. This often involves using a formulation that consists of 92–94% active ingredient with 6–8% excipients. These formulations require careful granulation, ensuring that the active ingredient is uniformly blended with the excipients to create a stable and efficient tablet.
5. Use of Super Disintegrants
For improved dissolution and flow properties, a combination of 50% intra-granular and 50% extra-granular disintegrants (like croscarmellose sodium) is often used. This strategy ensures that the tablet will break apart quickly once ingested, improving its bioavailability and ensuring fast disintegration when exposed to liquid.
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