# Stability of Paracetamol Amorphized by Co-Melting with Various Cellulose Derivatives
## 3 Results
### DSC Analysic
#### 3.1.2 Stability of Amorphous Form  
The second series of samples analyzed immediately after preparing the mixtures was re-analyzed after 2 months, and the third series after 4 months. The DSC curves obtained during these analyzes are shown in Figure 2. On the curve of the mixture containing 75% paracetamol with HPMC 86 analyzed after 2 and 4 months (Figure 2, a) shows a strongly broadened melting peak starting above 140 \({}^{\circ}\)C (Table 1). The signal of formation of metastable form III observed immediately after the first co-melting was practically invisible after 2 and 4 months. The melting enthalpy of form II after 2 and 4 months is higher than immediately after co-melting the mixture. In the case of a mixture containing 50% paracetamol with HPMC 86 (Figure 2, b), a small, strongly broadened and increasing over time peak was observed. However, a crystallization peak was not observed in the mixture containing 25% paracetamol (Figure 2, c).  
The signals observed in the DSC curves of paracetamol mixtures with HPMC 90 and HPMC 120 tested after 2 and 4 months (Figure 2, d,e,g,h) are very similar. The strong endothermic peak for mixtures at approximately 130 \({}^{\circ}\)C and then exothermic crystallization peak were observed. In mixtures containing 75% paracetamol, these signals were strong (Figure 2, d,g), and in mixtures with 50% they were small (Figure 2, e,h) but clearly marked. In the case of mixtures containing 25% paracetamol in a mixture with HPMC 90 (Figure 2, f) and HPMC 120 (Figure 2, i), no DSC peaks indicating crystallization and melting were observed.  
\begin{table}
\begin{tabular}{c c c c c c c c c c c c c c} \hline  & & & \multicolumn{3}{c}{**Mixture**} & \multicolumn{3}{c}{**Mixture**} & \multicolumn{3}{c}{**Mixture**} \\  & & & **with** & **HPMC 86** & & & **with** & **HPMC 90** & & **with** & **HPMC 120** & & **with** & **MC** \\ \hline \multicolumn{12}{c}{**PAR Content in Mixture**} \\ \cline{3-14}  & & & **75\%** & **50\%** & **25\%** & **75\%** & **50\%** & **25\%** & **75\%** & **50\%** & **25\%** & **75\%** & **50\%** & **25\%** \\ \hline \multirow{4}{*}{
\begin{tabular}{c} **PAR Content in Mixture** \\ \end{tabular} } & Enthalpy & & & & & & & & & & & & & & \\  & & & & & & & & & & & & & & & \\  & & & & & & & & & & & & &The shape of the DSC curves of paracetamol and MC mixtures obtained after 2 and 4 months (Figure 2, j-l) is similar. The curves of mixtures containing 75% (Figure 2, j) show an intense, broadened peak above 158 \({}^{\circ}\)C. For 50% mixtures (Figure 2, k), this peak is preceded by broad signals. An endothermic melting peak at approximately 160 \({}^{\circ}\)C of very low intensity, but interpretable, was also observed for mixtures containing 25% paracetamol (Figure 2, k).  
Figure 3 shows a two-dimensional scatter plot of PC1 and PC2 factors, calculated for the results of DSC tests performed 2 and 4 months after co-melting mixtures of paracetamol with polymeric cellulose derivatives.  
The PCA results created three clusters, with the main concentrating variable as the paracetamol content in mixture. The \"a\" and \"b\" cluster highlighted in red and green, respectively, concentrate the results obtained for mixtures containing 25 and 50% of paracetamol, while the orange \"c\" cluster corresponds to mixtures containing 75% of paracetamol. Clearly separated from the others each of the tested mixtures confirms that their compositions were different. These mixtures undergoing some modification after 2 and 4 months, but these differences were not significant because most mixtures were included to the same cluster, except of three ones which were located outside of specific cluster.  
Figure 2: DSC curves of paracetamol mixtures containing 75%, 50% and 25% of paracetamol (respectively) with HPMC 86 (a–c), HPMC 90 (d–f), HPMC 120 (g–i) and MC (j–l) obtained after 2 and 4 months.