*4.2.1 Thermal stability*

Thermal stability is a critical feature for any APD-API or APD-API co-crystal. However, most APD-APIs have low thermal stability, and modifying these APD-APIs into APD-API co-crystals has demonstrated to enhance overall stability [107]. Notably, APD-APIs that easily sublime at room temperature inevitably result in drug loss during manufacture and storage. According to Lu et al. [108], the conversion of APD-APIs into APD-API co-crystals such as 2,6-dihydroxybenzoic acid has greatly increased thermal stability, as evidenced by results of study using differential scanning calorimetry and the thermogravimetric analysis method. When compared with APD-API, dihydroartemisinin, which sublimes at a relatively low temperature, co-crystals such as 2,6-dihydroxybenzoic acid have a higher sublimation temperature above 100°C, indicating a better degree of thermal stability [108].
