## 4 Discussion  
The objective of the present work was to explore if the MCC shortcoming of losing the intensity of its binding power following reprocessing or reworking can be alleviated. This investigation was focused on applying immense compaction force using a roller compactor. In the present work, one of the most used excipients in preparations of pharmaceutical solid dosage forms was selected as the investigational model, that is, Avicel PH101. This MCC (Avicel PH-101) is the most commonly used grade in tablet manufacturing among different branded grades of MCC produced by FMC (FMC BioPolymer, Philadelphia, PA, USA). Furthermore, the present choice of Avicel PH-101 was primarily aimed to compare the obtained results with previously published research in which this grade was used [27, 28, 29, 30]. This may assist in the understanding of the mechanism underlying Avicel PH101 loss of binding in reworking during tablet making. It is worth mentioning that, as a spray-dried material, Avicel PH101 is highly porous with low bulk density which results in poor flowability, as is clear from Figure 2.  
Initially, the outcome of the Kawakita analysis gives a clear indication that once Avicel PH101 is subjected to certain roller compaction it hinders further compression. This finding is deduced from higher resistance of the granules under the applied compression force (1/_b_) and, concurrently, by the lower volume reduction for powders (_a_) and lower particle re-arrangement (_ab_) for powders  
\begin{table}
\begin{tabular}{l c c c c c} \hline \hline \multirow{2}{*}{**Powder Type**} & \multicolumn{5}{c}{**Kawakita Parameters**} \\ \cline{2-6}  & **Slope (I/a)** & **Intercept (I/_ab_)** & \(a\) & **1/_b_** & _ab_ \\ \hline Non-Compacted Avicel®  
resulting from a higher number of compaction cycles. This behavior is more likely to be attributed to physical modification resulting from the increase in density of granules with compacted cycle repetition. However, Kawakita analysis did not give any indication as to why the tablet crushing force underwent a decrease and then an increase when the compressed powder was made of compacted Avicel PH-101 comprising the 1 st (decrease), 2 nd (decrease), and the 3 rd (increase) compaction cycles. The compacts resulting from the first and second cycles resulted in similar values of crushing strength, indicating that compacts have similar properties under these two cycles because their porous structures stay within the same vicinity. This makes it necessary to test particle size, flow properties, and compression behaviors to clarify the increase in tablet crushing strength under a third compaction cycle. Initially, high compression/compaction pressures do not alter the chemical structure of microcrystalline cellulose [48]. The increase in the extent of plasticity of Avicel PH-101 (as indicated by the decrease in \(P_{Y}\) values) when the powder is compacted is more likely to be attributed to the presence of more deforming surfaces upon compaction. In the current case, densification upon processing of Avicel PH-101 via roller compaction is believed to be a major contributor to the extensive presence of new particle surfaces. In contrast, the decrease in \(\mathrm{D_{b}}\) values for powders comprising the 1 st and 2 nd compaction cycles highlights a notable difference in powder density as the compaction force is increased (Table 3). This behavior is most probably due to the difference in particle surface irregularities and pore sizes of the powder bed subjected to compression. In this regard, the 1 st and 2 nd compacted powders are made of larger granules with higher pore size (diameter) than non-compacted powder and the material under compaction preserves its plasticity (Figure 3 and Table 1). In addition, it can be interpreted in terms of low powder re-arrangement, as lower \(\mathrm{D_{b}}\) was depicted when granules become denser and larger upon compaction [49].