## 2 Materials and Methods  
### Kinetic Studies  
Pure RAM (100%) was purchased from Rolabo (Zaragoza, Spain, batch n\({}^{\circ}\): 11.PT24.01.02). HPLC-grade methanol, acetonitrile, formaldehyde and potassium dihydrogen phosphate were purchased from Merck, Darmstadt, Germany.  
Samples of RAM were weighted on analytical scale Satorius BP 2105. They were heated in thermal chambers WAMED KBC-125 W with automatic temperature and RH control (Wamed, Warsaw, Poland).  
The kinetic analysis was performed using a Shimadzu liquid chromatograph (Shimadzu Corporation, Kyoto, Japan) consisting of a Rheodyne 7125, 100 \(\upmu\)L. fixed loop injector, a UV-VIS SPO-6 AV detector, an LC-6A pump and a C-RGA chromatopac integrator. The following operating conditions were applied: mobile phase consisting of acetonitrile-aqueous phosphate buffer, pH 2.0; 0.035 mol/L (65:35 \(\mathit{v}\)/\(\mathit{v}\)) and stationary phase consisting of LiChrospher 100 RP-18 (size 5 \(\upmu\)m) 250 mm \(\times\) 4 mm I.D column. The chromatographic separation was isocratically performed at ambient temperature at a flow rate of 1.2 mL/min with the detector wavelength set at 215 nm. The injection volume was 20 \(\upmu\)L. The mobile phase had been filtered through a filter (0.22 \(\upmu\)m) and degassed by ultrasound prior to use.  
The employed HPLC method was revalidated in order to confirm its applicability for the assessment of the RAM stability profile under dry air conditions. The following validation parameters were determined: selectivity, linearity, sensitivity, precision and accuracy according to procedures described in our previous publication [15]. They were in agreement with ICH guideline Validation of analytical procedures: Text and methodology Q2 (R1) [25]. For that purpose, a calibration curve was constructed; limit of detection (DL), limit of quantification (QL), coefficient of variation (CV) and recovery were calculated. The procedures for revalidation are provided in the Supplementary Material (Supplement S1: HPLC validation procedures).  
The kinetic evaluation of RAM degradation was then conducted under stress conditions of elevated temperature, ranging from 353 K to 373 K and dry air (RH 0%). Samples of pure RAM (0.010 g) were analytically weighed into glass vials, placed into a sand bath and heated for different time intervals so as to induce degradation. Then, respective samples were dissolved in methanol to a total volume of 25.0 mL and filtered. The chromatograms were achieved. Basing on the chromatographic peaks areas, the contents of RAM and its degradation product were calculated (c) from the calibration curve. These results were plotted versus time (t) so as to construct kinetic curves: c = f(t) and kinetic equations. The kinetic model of the degradation was established by fitting the experimental data to the following theoretical equations: nucleation (power-law, Avrami-Erofeev, Prout-Tompkins), geometrical contraction (contracting area, contracting volume), diffusion (1D diffusion, 2D diffusion, 3D diffusion) and reaction-order (zero-order, first-order, second-order and third-order). The best fit, defined by the highest correlation coefficient, was identified. The degradation rate constants (k) were then calculated using least square method. Furthermore, thermodynamic parameters were evaluated based on the procedure described in our previous publication [15]. The relevant equations for the kinetic study procedures and thermodynamic calculations [26] are provided in Supplement S2: Thermodynamic parameters calculation.