*2.1. Materials*

Aquacoat ® ECD was donated from FMC BioPolymer, Newark, NJ, USA. Surelease ® E-7-19040 was given from Colorcon Inc., Harleysville, PA, USA. Parteck ® ODT was received from Merck KGaA, Darmstadt, Germany. SmartEx ® QD-50 was handed over from Shin-Etsu Chemical Co., Ltd., Tokyo, Japan. F-Melt C was purchased from Fuji Chemical Industry Co., Ltd., Toyama, Japan. Pearlitol ® Flash was a gift from Roquette, Lestrem, France. Magnesium stearate and methylene blue were acquired from POCh, Piekary Sl ˛ ´ askie, Poland. RUP was procured from Xi'An Kerui Biotechnology Co., Ltd., Xi'An, China.

#### *2.2. Preparation of ODMT*

A traditional tablet presser (Type XP1, Korsch, Berlin, Germany) with 3-mm punches was employed to manufacture ODMT by direct compression. In tableting bulk preparation, optimized spray dried microparticles with RUP prepared with EC aqueous dispersions selected during preliminary studies—urelease ® and Aquacoat ® ECD as a barrier coatings were utilized [17]. The conditions of the spray drying process were established experimentally: 85 ◦C, aspirator flow 98%, rate of flow 3.5 mL/min. E fficient barrier for masking the bitterness of drug enclosed in microparticles was obtained utilizing RUP:polymer ratio (0.5:1) with 6% EC concentration and this formulation was used for designing ODMT. ODMT with a mass of 14 mg and amount of microparticles corresponding to 0.5 mg of RUP per single tablet were assumed. The compositions of designed tableting masses utilized in the study are shown in Table 1. Prepared tableting blends were mixed manually for 30 s. To determine relevant conditions of the tableting process, various pressure force grades ranging from 0.6 to 1.2 kN were tested. Tablets with optimal properties that did not have a damaged surface of microparticles were obtained using a 0.9 kN (± 0.1) force. To simplify the formulation of ODMT, multifunctional co-processed mixtures were utilized. Co-processed mixtures are designed by processing several excipients to possess advantages that cannot be achieved by the simple physical mixtures of their components [18–24].


**Table 1.** Composition of orodispersible minitablets (ODMT) formulations.

#### *2.3. Flow Properties of Powders*

The tableting blends (Table 1) were subjected to preformulative quality assessment in accordance with pharmacopoeial requirements [25]. Each study was carried out in triplicate. A tapping apparatus (Electrolab ETD-1020, Mumbai, India) was utilized for the compressibility studies. The bulk and tapped densities were calculated as quotients of the weight of the powder to its volumes occupied before and after tapping and then the powder density index (Index Carr) and the powder flow index (Hausner's ratio) were calculated. To investigate powder flow time, 50 g of the sample was placed in the funnel with the outlet closed and after opening the valve, the flow of the whole sample through the funnel was measured [25].

#### *2.4. Evaluation of Morphology of ODMT*

Morphological structure was assessed utilizing scanning electron microscopy (Inspect ™S50, FEI Company, Hillsboro, OR, USA). Swatches were placed on adhesive tapes fixed to the surface of a special stand and gold sprayed. Tests were performed at room temperature, using various magnifications.

#### *2.5. Quality Assessment of ODMT*

#### 2.5.1. Uniformity of Weight and Thickness

Twenty randomly chosen ODMT were weighted individually, employing analytical balance (Radwag, Radom, Poland) [25]. The thickness was tested with calibrated digital caliper utilization (Beta 1651DGT, Milan, Italy).
