dddd, Nov d

2:30 TT – 3:30 TT

** Purpose: **The intent of this study was to evaluate the effect of wet-granulation process parameters (mixing/kneading time, amount of water added, and water addition rate) on the critical quality attributes (CQAs) of a tablet formulation of a novel oncology agent, viz. particle size distribution (PSD), bulk density/tapped density, loss on drying (LOD) and tablet compactibility. These CQAs can impact compression which in turn can affect target product attributes such as content uniformity and dissolution. Understanding how the process parameters affect these CQAs is important to have better control over the process and to ensure that the process is robust.

However, the amount of water and kneading time did have an effect on the bulk density and tapped bulk density (p = 0.001). Increases in the amounts of water and kneading time from low to high caused increases in bulk density by ~13% and tapped density by ~7%.

Figure 2 Pareto Chart for bulk/tapped density

Of the three parameters studied, the solution addition rate did not have any effect on its own (p > 0.1). However, when combined with amount of water and kneading time, it did have effect (p = 0.028) on particles larger than 600 microns (% retained on 30 mesh screen).

For compressed tablets, a linear relation between the logarithm of tensile strength and porosity was obtained. This relation was fitted to the Ryshkewitch-Duckworth equation (lnσ = lnσ – k*ε) where σ is tensile strength, σ0 is tensile strength at zero porosity and ε is the tablet porosity (Figure 3). This equation represents exponential decay of tensile strength with increase in porosity. Using this equation, tensile strength at zero porosity was calculated, which represents the maximum compaction for a tablet. It was found that the amount of water and kneading time had a significant effect (p = 0.03) on the maximum tensile strength of the tablets.

- CP
Chinmay Pathak

– Development Scientist, Catalent Pharma Solutions - CP
Chinmay Pathak

– Development Scientist, Catalent Pharma Solutions - CP
Chinmay Pathak

– Development Scientist, Catalent Pharma Solutions - FM
Francis Muller

– Senior Director, Incyte Corporation, Chester Springs - RS
Raj Sheth

– Incyte Corporation - CH
Christin Hollis

– Catalent Pharma Solutions - CP
Chinmay Pathak

– Development Scientist, Catalent Pharma Solutions

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