*2.2. Substances*

In order to analyze different crystal shapes, potassium dihydrogen phosphate (KH2PO4) and thiamine hydrochloride were used.

KH2PO4 grew bipyramidal, prismatic shaped crystals, depicted in Figure 3a, and thiamine hydrochloride monohydrate grew needle-like shape, as depicted in Figure 3b.

**Figure 3.** (**a**) KH2PO4 crystals; (**b**) Thiamine hydrochloride monohydrate crystals captured by the shadowgraphic probe during the experiments.

KH2PO4 grows resilient crystals, that are very suitable for validation purposes, because they do not tend to break in a bypass, during filtration, or sieving. In order to design the crystallization process, the solubility and the kinetics must be known, especially because KH2PO4 tends to form longer or shorter body prisms, depending on the operation conditions. The crystallization kinetics in aqueous solutions and the solubility are well known and reported [62,63]. The latter can be described by the following polynomial expression:

$$\begin{array}{rcl} \mathbb{C}\_{\text{srt}}(T) \left[ \text{wt.}-\text{\textquotedblleft} \right] &=& 15.24 \text{ wt.}-\text{\textquotedblleft} + \text{ } 2.06 \times 10^{-1} \frac{\text{wt.}-\text{\textquotedblleft}\_{0}}{\text{\textquotedblleft C}}T + 1.01\\ &\times 10^{-2} \frac{\text{wt.}-\text{\textquotedblleft}\_{0}}{\text{\textquotedblleft C}}T^{2} - 1.45 \times 10^{-4} \frac{\text{wt.}-\text{\textquotedblright}\_{0}}{\text{\textquotedblleft C}}T^{3} + 1.23\\ &\times 10^{-6} \frac{\text{wt.}-\text{\textquotedblright}\_{0}}{\text{\textquotedblleft C}}T^{4} \end{array} \tag{1}$$

Thiamine hydrochloride exists in five solid-state forms, according to the literature [64,65]. The desired form in industrial applications is a pseudo-monohydrate that crystallizes in contact with water, and contains 0.5 to 1 mole water per mole thiamine in the needle-like shaped crystals (see Figure 3b).

However, this monohydrate is metastable at ambient conditions and converts fast into the thermodynamic stable thiamin hydrochloride hemihydrate. Hence, the solid-liquid equilibrium of the pseudo-monohydrate is difficult to measure, and therefore barely investigated [65,66]. Fortunately, data of the less-soluble thiamine hydrochloride hemihydrate in some binary solvents are reported, and therefore the experimental design was based on data of a binary water/ethanol mixture [67]. Some physiochemical properties of the thiamin hydrochloride and KH2PO4 are shown in Table 1.


**Table 1.** Properties of the utilized substances KH2PO4 and thiamin hydrochloride.
