*4.2.2 Solubility*

APD-APIs are often either slightly soluble or insoluble, which limits their application as biopharmaceuticals. The modification of these APD-APIs into co-crystals may be crucial, as several studies have shown that co-crystals can maintain stability while also enhancing solubility [109]. In most circumstances, it has been noted that

#### *Co-Crystallization of Plant-Derived Antimalarial Drugs: An Alternate Technique for Improved… DOI: http://dx.doi.org/10.5772/intechopen.106200*

selecting highly soluble coformers can increase co-crystal solubility. For example, in the production of certain APD-APIs co-crystals, extremely soluble coformers such as succinic acid and benzoic acid have been used [110].

#### *4.2.3 Hygroscopicity*

Because of the presence of free functional groups such as hydroxyl groups, most APD-APIs, including phenols, are very unstable at high relative humidity (have high hygroscopicity) [111]. Wong et al. [112], on the other hand, claim that the interaction between APD-API and their respective coformers during crystallization processes increases stability at high relative humidity. Curcumin-resorcinol co-crystals, for example, have been demonstrated to be very stable at high (95%) relative humidity as compared with curcumin, which quickly absorbs moisture at 75% relative humidity [113]. The interaction between the APD-API functional groups and those of the coformers, resulting in intermolecular interactions, is correlated to the stability of APD-API co-crystals at high (95%) relative humidity (low hygroscopicity) [114]. The presence of these intermolecular connections in APD-API co-crystals inhibits the interaction between moisture and APD-API functional groups [111]. This basically means that when the interactions between coformers and APD-APIs increase, the barrier to moisture absorption of APD-API co-crystals falls dramatically.

**NB** the other important properties of APD-APIs, which are modified in order to improve their efficacy through co-crystallization production, include bioavailability, dissolution, and tabletability [112].
