## 3 Results
### Kinetic Mechanism of RAM Degradation under RH 0%  
The content of RAM in the stressed samples was established by the validated HPLC and plotted versus time of exposure. The content was expressed as the percentage of the remaining drug concentration, with 100% of RAM corresponding to t = 0 h. The logarithmic kinetic curves were thus achieved (Figure 2). Then, they were transformed into semilogarithmic plots, and the straight lines were obtained for each sample series at each temperature, as depicted in Figure 2.  
Figure 1: HPLC chromatogram for: (**A**) undegraded RAM in solid state; (**B**) partially-degraded RAM (t = 20 h, 373 K); (**C**) RAM after complete degradation (t = 90 h, 373 K). Figure 2 demonstrates kinetic curves for RAM degradation at four different temperatures. It also demonstrates one logarithmic plot for a series at T 373 K as an example. For each experimental series, the gradual loss of RAM in stressed samples was confirmed. Furthermore, the higher the temperature, the more rapid the reaction was, as expressed by increasing slopes of the kinetic curves. The dots represent the contents of RAM (c%) in respective samples stressed under denotated temperatures for increasing time intervals. The most rapid loss of RAM was observed at the highest temperature tested (T = 373 K), as the corresponding concentrations established by validated HPLC were the lowest. At lower temperatures, the decrease in RAM content in stressed samples was relatively less rapid. The F-test was performed for each linear regression and the obtained \(p\)-values confirmed that the correlations were significant and slopes were different from zero (Supplementary Material Table S2). Therefore, it was shown that the loss of RAM was proportional to time of exposure and its rate positively correlated with temperature level. Consequently, the reactions were found to follow first-order kinetics, irrespective of the temperature level, confirmed by the high correlation between the experimental data (Table 1). They were described by the following kinetic equation:  
\[\ln c_{t}=\ln c_{0}-k\t\]  
where \(c_{t}\) and \(c_{0}\) are concentrations of RAM in time t and 0, respectively, k is the first-order rate constant (s\({}^{-1}\)). The magnitude of k was then calculated as it corresponds to the slope of the obtained plot c = f(t) in the following manner: a = \(-\)k [26]. The kinetic and thermodynamic parameters of the reaction of RAM degradation were provided in Table 1. The corresponding raw data and their statistical analysis are provided in Supplement S4: Kinetic study results (Table S2). \begin{table}
\begin{tabular}{c c c c} \hline
**T [K]** & **k \(\pm\)****A**k [s\({}^{-1}\)]** & **r** & **Linear Arrhenius Relationship** & **Thermodynamic** \\  & & & **f(1/T) = lnk\({}_{i}\)** & **Parameters** \\ \hline
353 & (5.340 \(\pm\) 0.395) \(\times\) 10\({}^{-7}\) & \(-\)0.997 & a = \(-\)20,943.07 \(\pm\) 5564.7 & E\({}_{a}\) [k]/mol] = 174.12 \(\pm\) 46.2 \\
358 & (1.760 \(\pm\) 0.176) \(\times\) 10\({}^{-6}\) & \(-\)0.994 & s\({}_{a}\) = 1748.81 & A\(\mu\)H [k]/mol] = 171.65 \(\pm\) 48.7 \\
363 & (3.289 \(\pm\) 0.431) \(\times\) 10\({}^{-6}\) & \(-\)0.992 & b = 45.03 \(\pm\) 15.4 & AS [J/mol\(\cdot\)K] = 0.12 \(\pm\) 12.5 \\
373 & (1.396 \(\pm\) 0.133) \(\times\) 10\({}^{-5}\) & \(-\)0.997 & s\({}_{b}\) = 4.83 & r = \(-\)0.993 \\  & & & F = 155.3 & \\  & & & DFn, DFd = 1.2 & \\  & & & \(p\) = 0.0064 & \\ \hline \end{tabular}
\end{table} 
Table 1: Kinetic and thermodynamic parameters of solid state RAM degradation under RH 0%. Figure 2: Semi-logarithmic plots c\({}_{t}\) = f(t) describing degradation of RAM in solid state under dry air conditions at different temperatures. Table 1 demonstrates the calculated degradation rate constants (k) for RAM at four different temperatures. The provided k values are specific to the conditions at which they were obtained, and they describe the rate at which the reaction of RAM decay occurred.