2.5.3. Drug Content

HPLC apparatus (Agilent Technologies 1200) equipped with Waters Spherisorb ® 5 μm ODS1 4.6 × 250 mm column (Waters Corporation, Milford, CT, USA) was applied to evaluate RUP content uniformity for individual ODMT. As a mobile phase methanol:phosphate bu ffer pH = 3.0 (35:65, v/v) was utilized (isocratic elution). Flux was established as 1.0 mL/min and wavelength as 245 nm. Bu ffer was composed of NaH2PO4 and water, adjusted to pH = 3.0 by H3PO4. Standard calibration curve was linear in the range of 1–100 μg/mL and the correlation coe fficient R<sup>2</sup> was 0.999. The studies were carried out in triplicate [26–28].

#### *2.6. Disintegration Time Assessment*

#### 2.6.1. In Vivo

The study was carried out by six probands (Research Ethics Committee at Medical University of Białystok approval number R-I-002/438/2016) in the following stages: oral cavity rinsing with water, placing ODMT in the mouth without chewing until disintegration, splitting out. The time needed for the total disintegration in the mouth was recorded.

#### 2.6.2. Petri Dish

Petri dish having a diameter of 7 cm was filled with 4 mL of phosphate bu ffer pH = 6.8 imitating natural spit (composing of Na2HPO4; KH2PO4 and water; adjusted to pH 6.8 by 1-M NaOH) [17] and single ODMT was put in the center. The test was repeated for 6 tablets from each batch. Time for the tablet to completely disintegrate into fine particles was measured.

## 2.6.3. Texture Analyzer

The study was conducted with a texture analyzer (Stable Microsystems, Godalming, UK) with an ODT disintegration time rig (Figure 1). Single ODMT was attached to the bottom of the probe with double-side adhesive tape. The ODMT was immersed in the medium (4 mL of phosphate bu ffer pH = 6.8 imitating natural spit) until it comes in contact with the perforated bottom of the container. The test was repeated for 6 tablets from each batch.

 

**Figure 1.** Schematic illustration of disintegration time rig of the texture analyzer.
