## 2 Materials and Methods
### Methods  
#### 2.2.1 Physical and Chemical Characterization  
_The FTIR analysis_ was performed using a JASCO FTIR 410 spectrophotometer. A mixture of 1 mg sample and 500 mg KBr of IR purity was prepared. The mixture was homogenised in an agate mortar. Then, the mixture was dried at 105 \({}^{\circ}\)C for one hour and cooled at room temperature. 500 mg of obtained sample was introduced into the hydraulic press and compressed. Finally, a perfect transparent tablet was obtained, without material inclusion. It was placed inside the spectrophotometer and its spectrum was recorded. The obtained spectra were compared with a standard reference. The FTIR spectra are presented in transmittance (%).  
_The thermal experiments_ were performed on a Mettler Toledo DSC 853e differential scanning calorimeter, within the temperature range 30-250 \({}^{\circ}\)C. The thermal DSC curves were recorded in a nitrogen atmosphere with a flow rate of 80 mL.min\({}^{-1}\) and at a heating rate of 10 K\(\cdot\)min\({}^{-1}\). The samples were held in aluminium crucibles with a pinhole in the lid. The sample mass was approximately 2 mg.  
_Optical microscopy_ analysis was performed using a NIKON(r) Eclipse 50i optical microscope (Natori City, Miyagi Prefecture, Japan). The lenses were used were 4\(\times\), 10\(\times\), 40\(\times\) and 100\(\times\). The obtained images were used to measure particle diameters and surface areas using the MoticImagesPlus(r) 2.0 ML digital microscopic imaging program.  
_Determination of felodipine particle size_Particle size analysis was performed using two methods: (i) by direct microscopic examination with computerised image processing using specialised software and (ii) by the sieving and sorting method.  
_(i) Microscopic evaluation_  
In the optical microscopic examination, the particle sizes were measured using the MoticImagesPlus(r) program. Measurements were made in multiple fields of view and the particles' diameters and appearance were determined. Statistical data were processed with the XLSTAT(r) program.  
_(ii) Sieving and sorting_ method was performed on standardised RETSCH analytical sieves from the AS 200 Basic apparatus, equipped with sieves of mesh sizes 500 \(\upmu\)m, 300 \(\upmu\)m, 100 \(\upmu\)m, 75 \(\upmu\)m, 53 \(\upmu\)m and 32 \(\upmu\)m. A quantity of substance (25 g) was transferred to the upper sieve, the time was set to 15 min and the vibration amplitude to 1.5 mm. In the end, the residual materials on each sieve were weighed on a Mettler Toledo AT261 balance (0.01 mg sensitivity).  
_The bulk and tapped density_ were determined using Vankel Tap Density Tester, produced by Vankel Industries Inc., Los Angeles, CA, USA. The flowability and compressibility properties of the powder were established by calculating the Hausner ratio (HR) and Carr Index (CI). The bulk density represents the ratio between the analysed powder mass (100 g) and the occupied volume from a graduated cylinder. The tapped volume is measured after subjecting the same amount of powder to a different number of mechanical shocks. The Hausner ratio (HR) is calculated as the ratio between tapped and bulk density, a value above 1.25 being considered a low flowability indicator. The Carr index is given by Equation (1)  
\[\text{CI}\%=\frac{(\text{tapped density}-\text{bulk density})\times 100}{\text{tapped density}} \tag{1}\]  
where values greater than 25% represent low flowability and compressibility attributes and values below 15% expresses good flow and compression qualities [17].