Novel use of monodisperse granules to deconvolute impacts of granule size versus granule solid fraction on tablet tensile strength

• Tablet tensile strength (TS) is important for integrity and its performance in vivo.
• Monodisperse granules were used to develop a mechanistic understanding of tablet TS.
• Granule solid fraction (SF), but not granule size, was found to impact tablet TS.
• Apparent granule deformation potential was defined as (Tablet SF)–(Granule SF).
• Tablet TS increases linearly with the apparent granule deformation potential.

Dry granulation processes such as roller compaction produce granules that are poly-disperse in both size and solid fraction, making it difficult to deconvolute the effect of granule size and solid fraction on tablet compaction. To overcome this issue, small cylindrical compacts of microcrystalline cellulose are used as model dry granules which have the advantage of being monodisperse in both size and solid fraction. In addition, size and solid fraction of monodisperse granules can be independently varied and precisely controlled. Monodisperse granules of microcrystalline cellulose with solid fractions in the range 0.4–0.8 were compressed to give tablets with solid fractions in the range 0.72–0.84. Tablet tensile strength was measured by diametrical compression of the tablets. Results showed a strong linear relationship (with negative slope) between the tablet tensile strength and granule solid fraction. Tensile strength increased linearly with the apparent deformation potential (difference between the tablet solid fraction and initial granule solid fraction) for all tablet solid fractions. Results also showed that contrary to popular perception, granule size had no statistical impact on the tablet tensile strength.

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