The hygroscopicity of KB-0742 (HY-137478) would indeed be reduced, but its water solubility would also be poorer. If the customer is conducting cell experiments, an alternative may be considered. However, for animal experiments, the more water-soluble salt form, KB-0742 Dihydrochloride (HY-137478A), is highly recommended for easier dissolution.

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The ability to draw moisture from the atmosphere is critical in maintaining the composition, stability, and management of pharmaceutical products. As a result, free base drug forms exhibit less hygroscopicity relative to their respective salt forms, which is due to crystal lattice structures and ionic interactions. Numerous salts deliquesce and are largely hygroscopic despite being crucial since their ionic lattice interacts comfortably with water molecules, facilitating increased moisture adsorption. It is important to note that hydrogen bonding sites of salts are more polar and have a higher affinity for water, unlike free base forms with a less polar structure (Chokshi & Zia, 2004).

Consequently, salts aggregate higher moisture under regulated humidity, which intensifies the likelihood of deliquescence and easier degradation (Kumar et al., 2021). Additionally, salts, as opposed to the free base forms, have consistently shown higher moisture consumption isotherms in hygroscopicity studies using dynamic vapor sorption (DVS) methodology (Taylor et al., 2020).  In this context, I would anticipate that KB-0742 in its free base form would exhibit lower hygroscopicity compared to the dihydrochloride salt form, which would considerably benefit the production strategy. This lower hygroscopicity would improve ease of processing, shelf life, and obviate the need for unique storage or packaging (Araujo et al., 2019). This analysis builds the context, providing evidence that free-base pharmaceutical forms exhibit less hygroscopicity than their respective salts.

References:

Araujo, G. L. B., Oliveira, J. V., & Carvalho, R. A. (2019). Influence on salt Preparation: Hygroscopicity and stability of pharmaceutical compounds. J. Pharm. Sci., 108(1), 412–420. https://doi.org/10.1016/j.xphs.2018.08.078

Brittain, H. G. (2016). Polymorphism in pharmaceutical solids. In Pharmaceutical Salts and Co-crystals (pp. 47–84).

Chokshi, R. J., & Zia, H. (2004). Crystal Habit and Particle Size in Drug Product Design. Pharm. Technol., 28(12), 50–68.

Kumar, S., Sharma, R., & Singh, S. (2021). Hygroscopicity Assessment of Free Base and Hydrochloride Salt Form of Kinase Inhibitors: A Novel and Comprehensive Approach. Int. J. Pharm., 599, 120363.

Taylor, L. S., Zografi, G., & Mauer, A. M. (2020). Moisture Sorption and Hygroscopicity of Pharmaceutical Solids. J. Pharm. Sci., 109(3), 1083–1096.