## 3 Results and Discussion  
### Structural Characterization of ARP  
ARP belongs to the substances which represent conformational polymorphism [10; 16]. In this study, form III of ARP, which is determined as metastable in the entire temperature range and is marketed in medicinal products the most often, was used in the formulation process. [PERSON] and coworkers revealed the conversions between crystalline forms of ARP using solutions of form III in water and mixtures of water with acetonitrile, ethanol, methanol, or tetrahydrofuran [10; 16]. HME utilizing the thermoplastic properties of polymers and eliminating the solvent was applied. [PERSON] and coworkers also pointed out that heating form III above the \(T_{m}\) and keeping it at about 145 \({}^{\circ}\)C can favor conversion to form I [16]. Therefore, carrying out the formulation process below the \(T_{m}\) of ARP should guarantee the maintenance of form III, and thus the bioavailability and stability of the drug substance. In this study, the structural and thermal characterizations were made for raw ARP and 105 \({}^{\circ}\)C-treated ARP to determine the HME conditions (Figures 1-4, Tables 1 and 2). Figure 1: Diffraction pattern of raw ARP and 105 \({}^{\circ}\)C-treated ARP. \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{2}{*}{**Sample**} & \multirow{2}{*}{**
\begin{tabular}{c} **\(T_{m1}\)** \\ **(\({}^{\circ}\)C)** \\ \end{tabular} } & \(\Delta H_{1}\) & \(T_{m2}\) & \(\Delta H_{2}\) & \(T_{cr}\) & \(\Delta H_{cr}\) \\  & & (\({}^{\circ}\)C) & (/g) & (\({}^{\circ}\)C) & (/g) & (\({}^{\circ}\)C) & (/g) \\ \hline \multirow{4}{*}{Raw ARP} & First & _ND_ & _ND_ & 140.0 & 95.7 & _ND_ & _ND_ \\  & Second & 134.4 & 7.2 & 140.0 & 90.1 & 94.4 & 91.8 \\  & Third & 134.7 & 7.6 & 139.9 & 90.5 & 95.6 & 90.2 \\  & Fourth & 134.8 & 7.5 & 139.9 & 90.7 & 96.6 & 90.2 \\  & First & _ND_ & _ND_ & 140.1 & 95.7 & _ND_ & _ND_ \\  & Second & 134.6 & 7.6 & 139.9 & 91.8 & 95.2 & 91.8 \\  & Third & 139.6 & 5.4 & 139.6 & 91.1 & 95.6 & 90.9 \\  & Fourth & 134.7 & 6.5 & 139.9 & 90.5 & 96.6 & 90.2 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: The thermal parameters characterizing raw ARP and 105 \({}^{\circ}\)C-treated ARP during the four heating runs. Figure 3: HSM images of 25 \({}^{\circ}\)C-treated ARP, 105 \({}^{\circ}\)C-treated ARP, 138 \({}^{\circ}\)C-treated ARP, and 140 \({}^{\circ}\)C-treated ARP. Figure 2: The DSC heating curves for raw ARP for the first (**a**), second (**c**), third (**e**), and fourth (**g**) heating runs. The DSC cooling curves after the first (**b**), second (**d**), third (**f**), and fourth heating runs (**h**). The DSC heating curves for 105 \({}^{\circ}\)C-treated ARP for the first (**i**), second (**j**), third (**k**), and fourth heating runs (**l**). In the XRD study, form III of ARP was confirmed according to the manufacturer's declaration (Zhejiang Huahai Pharmaceutical Co., Ltd., Linhai China City, China). The characteristic peaks for form III, including 9.51\({}^{\circ}\), 14.32\({}^{\circ}\), 16.93\({}^{\circ}\), and 22.05\({}^{\circ}\), were revealed for both raw ARP and 105 \({}^{\circ}\)C-treated ARP. Moreover, the spectrum for the 105 \({}^{\circ}\)C-treated ARP sample did not reveal changes, which may confirm the lack of a phase transition (Figure 1 and Table 1). A DSC study was performed to potentially provide further information about possible changes during the formulation process (Figure 2 and Table 2). Four heating runs of raw ARP and 105 \({}^{\circ}\)C-treated ARP samples were carried out. Additionally, raw ARP cooling curves were also monitored. Two DSC heating runs for raw ARP showed typical effects for crystalline substances. Analysis of the first and second heating runs revealed the melting point at 140.0 \({}^{\circ}\)C (95.7 J/g) and the crystallization effect at 94.4 \({}^{\circ}\)C (91.8 J/g), respectively (Figure 2 and Table 2). The value of the \(T_{m}\) from the first heating run reflected the \(T_{m}\) obtained by [PERSON] and coworkers for form III [16].