*2.7. Tablets Characterization*

Appearance and morphologic analysis: the regularity of the tablets' appearance was checked by visual inspection. The morphology of the tablets' surface was examined more in detail by ESEM analysis.

Weight uniformity: 20 tablets randomly taken from the batch were individually weighed (Mettler XP2003S balance, Mettler Toledo, Greifensee, Switzerland). The mean tablet weight, and the relative CV percentage values were then determined.

Hardness: determined using a Schleuniger Hardness Tester mod 6D as crushing force (N). Tensile strength was also calculated to eliminate the possible effects of variations in tablet thickness on the measured crushing force;

Disintegration time: evaluated using the T2 221 Erweka disintegration apparatus (Erweka GmbH, Langen, Germany) at 37 ± 0.5 ◦C in pH 7.4 phosphate buffer;

Dissolution test: performed using a USP Paddle apparatus (Sotax AT7, Sotax, Thun, Switzerland). Tablets were added to 900 mL of pH 7.4 phosphate buffer solution thermostated at 37 ± 0.5 ◦C, at a stirring rate of 75 rpm. The concentration of dissolved drug was UV-monitored at 300 nm (Lambda 2 spectrophotometer, Perkin Elmer, Waltham, MA, USA). Each test was simultaneously carried out on six samples. Dissolution efficiency (DE) was calculated from the area under the dissolution curve at time t and expressed as a percentage of the area of the rectangle described by 100% dissolution in the same time [50]. Percent of drug dissolved and DE values were analyzed by one-way analysis of variance (ANOVA) followed by the Student–Newman–Keuls multiple comparison post-test (Graph Pad Prism 4.0 program, San Diego, CA, USA). Differences were considered statistically significant when *p* < 0.05.

#### **3. Results and Discussion**
