**5. Challenges and opportunities associated with development of co-crystallized antimalarial drugs from APD-APIs**

Notably, APD-APIs are divided into two categories: (1) potential compounds for natural medicine production and (2) templates for artificially synthesized pharmaceuticals [115]. The quest for novel plant-derived antimalarial drugs, as well as the development of phytomedicines in general, is, however, inherently associated with two major obstacles, (1) existence of extremely active plant compounds with complicated molecular structures, where no feasible industrial production is envisaged, and (2) presence of APD-APIs with relatively reduced activity yet with relatively simple molecular structures, for which artificial production could be conducted [115, 116]. With notable examples of naturally occurring ADP-APIs, the development of novel antimalarial drugs is without. Although various powerful plant-derived antiplasmodial compounds have been documented, the majority of them have only been assessed in vitro, with few being evaluated for toxicity and even fewer being evaluated in vivo [117, 118]. Furthermore, most of them seem to be present in low quantities in plants and are frequently found as part of complicated composites, making separation and processing extremely costly. Among other factors, scientific evaluation of traditional ADP-APIs is limited by paucity of ethnobotany information [115, 117].
