*2.8. Dissolution Studies*

Dissolution studies of theophylline and theophylline squarate trihydrate were carried out using water MilliQ (pH 5.5) at room temperature. 6 suspensions at a concentration of 1.5 mg/mL were prepared for both theophylline and theophylline squarate trihydrate. Each suspension corresponds to a different time point (0–2 min–4 min–6 min–8 min–10 min). From each sample, 200 μL were taken at the corresponding time point and filtered. 20 μL from each taken solution were then diluted (1:10) with H2O and injected.

Ultra-high-performance liquid chromatography with ultraviolet detection (UHPLC-UV) was used for quantitative analysis of the dissolved drug which absorbs UV-light in the range of 200–290 nm with an absorbance maximum at 254 nm. UHPLC-UV analysis was conducted on a Waters Acquity UPLC system (Milford, MA, USA) that was connected to a diode array detector and equipped with a reversed phase Kinetex® EVO C8 LCcolumn (100 × 2.1 mm; particle size 1.7 <sup>μ</sup>m; pore size 100 Å, Phenomenex®). The mobile phase consisted of 25 mM of ammonium formiate buffer (pH 3) and 0.1% formic acid in acetonitrile, the flow rate was 0.5 mL/min and the column oven was set to 50 ◦C. The injection volume was 2 μL.
