Discriminate the Differences Between Surface Water and Channel Water in the Formation of Solvates

Discriminate the differences between Surface water and Channel water in the formation of solvates

Yumin Liu^1,2, Dandan Han^1,2, Jingkang Wang^1,2, Junbo Gong^1,2*

¹ National Engineering Research Center of Industry Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China;

² The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin, China;

E-mail address: liuyumin@tju.edu.cn     junbo_gong@tju.edu.cn ^*

Abstract

Solvates are defined as Active Pharmaceutical Ingredients (APIs) solids which incorporate one or more solvent molecules in the crystal lattice or channel to form new crystalline substances. Converting the drugs into hydrophilic solvates can help to improve the solubility in water and increase drug bioavailability. Meanwhile, it also can improve the stability of drugs, thus facilitating the formulation and storage of the drugs. There are four binding modes between compounds and solvents, just presented in the following Figure 1. Liquid inclusions and incorporation into the lattice are composed of solvates. With the increased incidence of solvate formation, it is essential to get a comprehensive understanding of their structure, physical stability, and the implication of de-solvation on the properties of the APIs. Hydrate are the most abundant solvates, owing to the high propensity of water to be entrapped in the lattice of APIs, with its small size and tendency to form multi-directional hydrogen bonds. Pharmaceutical solids may come in contact with water during processing steps, such as crystallization, lyophilization, spray-drying, wet granulation, or aqueous film-coating, and they may be exposed to humid air during storage. Absorbed water molecules may reside on crystal surfaces, in crystal channel, or in crystal lattice structures which can change the packing in the unit cell. Surface water and channel water is quite different from each other. Without a doubt, we can utilize SXRPD to discriminate that differences between them. But in our laboratory,   several other offline analytical techniques, such as XRPD, TGA and DVS, were also adopted to distinguish it and achieved remarkable results.

Fig.1 Different principles of solvent associations with crystalline solids