2.6.4. Wettability

The wettability test was carried out according to Stoltenberg and Breitkreutz [29]. A 96-well plate (Biologix Group Limited, Lenexa, KS, USA) was used and a cellulose filter disc was placed in each well, which was then moistened by adding 20 μL of 0.3% aqueous solution of methylene blue. The time from placing the ODMT on moistened paper to complete coloring of the MT matrix was noted.

#### 2.6.5. Differential Scanning Calorimetry

RUP raw material (API), microparticles placebo (MP AQ placebo, MP SUR placebo), microparticles (MP AQ RUP, MP SUR RUP), ODMT placebo (F1, F5, F9, F13), ODMT with pure RUP (F2, F6, F10, F14) and ODMT with RUP enclosed in SUR MP (F3, F7, F11, F15) and AQ MP (F4, F8, F12, F16) were tested using thermal analyzer system (DSC Mettler Toledo, Greifensee, Switzerland). Swatches were accurately weighed (5 mg), inserted in pans made of aluminum, then warmed up to 300 ◦C with 10 ◦C/min rate with 20 mL/min flow of nitrogen.

#### *2.7. Evaluation of Taste Masking E*ff*ectiveness*

#### 2.7.1. In Vivo

The study was conducted in accordance with the Declaration of Helsinki and the protocol was approved by the Ethics Committee of Medical University of Białystok approval number R-I-002/438/2016. The efficiency of taste masking level was tested by six probands undergoing a test conducted as follows: five ODMTs were placed in the oral cavity for 30 s (the maximum time to dissolve/disintegrate in accordance to FDA guidelines [30]), spitted and mouth were rinsed with water. Sensory evaluation was marked as follows: 0—no bitterness, 1—slightly bitterness, 2—moderately bitterness, 3—significant bitterness. Before the experiment was carried out, the participants were chosen on the basis of sensory sensitivity test, utilizing four main flavors [31].

#### 2.7.2. RUP Dissolution

RUP dissolution was carried out in apparatus II (paddle) (Erweka Dissolution Tester DT 600HH, Heusenstamm, Germany) with phosphate buffer (pH 6.8, 50 mL) imitating natural spit in following conditions: 75 rpm and 37 ◦C (+/−0.5). The quantity of dissolved RUP was assessed as pointed in 2.5.3.

#### 2.7.3. Electronic Tongue

#### Reagents and Membrane Materials

Analytical reagen<sup>t</sup> grade chemicals and purified water with 0.07 μS/cm conductivity (Elix Advantage System Mili-Q plus Milipore, Spittal an der Drau, Austria) were used. The membrane consisted of poly(vinylchloride) (PVC) (Tarwinyl, Tarnów, Poland); bis(2-ethylhexyl) sebacate (DOS), and o-nitrophenyl octyl ether (o-NPOE) (Fluka, St. Gallen, Switzerland); potassium tetrakis [3,5-bis(trifluoromethyl)phenyl]-borate (KTFPB), tridodecylmethylammonium chloride (TDMAC), 1-dodecylpyridinium chloride (DDPC), (Sigma—Aldrich, St. Luis, MO, USA), and potassium tetrakis(p-chlorophenyl)borate (KTpCPB) (Fluka, St. Gallen, Switzerland); calix[6]arene-hexaacetic acid hexaethylester (amine ionophore I) (Fluka, St. Gallen, Switzerland), and 3-mercapto-5-/2-hydroxynaphthyl-azo-triazole (METRIAN) (Department of Drug Chemistry, Medical University of Lublin, Poland).
