2.2.9. Preparation of Surfactant-Coated Nano Co-Crystals via a Pseudo One-Solvent Bottom-Up Method

Surfactant-coated nano co-crystals were prepared as described in Section 2.2.1. Design Expert® software version 8.0.71, Stat-Ease Inc. (Minneapolis, MN, USA) was used to generate experiments for a general factorial experimental design and the process factors investigated are listed in Table 1. The surfactants were added to the aqueous phase with the exception of Span® 80, which was dissolved in methanol. The solutions were rapidly injected into a pre-cooled conical flask incubated at 4 ◦C ± 2 ◦C in an ice bath. A sonication output of 50 kHz ± 6 kHz was applied to the solution for 20 min using a Branson® 8510E-MT ultrasonic bath (Danbury, CT, USA). The NCC suspension that was produced was characterized within 24 h of preparation. Characterization of the NCC included ZP, PDI, PS and FTIR, Raman spectroscopy, DSC, PXRD and EDX-SEM. The concentration of each of the surfactants was 0.5%, 1% and 2% *w*/*v* of the total volume used (Table 1).


**Table 1.** Summary of general factorial experiments.
