In this work, a novel polysaccharide-based chiral stationary phase, cellulose tris(4-chloro-3-methylphenylcarbamate), also called Sepapak 4 has been evaluated for the chiral separation of amlodipine (AML) and its two impurities. AML is a powerful vasodilatator drug used for the treatment of hypertension. Capillary columns of 100 μm id packed with the chiral stationary phase were used for both nano-LC and CEC experiments. The optimization of the mobile phase composed of ACN/water, (90:10, v/v) containing 15 mM ammonium borate pH 10.0 in nano-LC allowed the chiral separation of AML and the two impurities, but not in a single run. With the purpose to obtain the separation of the three pairs of enantiomers simultaneously, CEC analyses were performed in the same conditions achieving better enantioresolution and higher separation efficiencies for each compound. To fully resolve the mixture of six enantiomers, parameters such as buffer pH and concentration sample injection have been then investigated. A mixture of ACN/water (90:10, v/v) containing 5 mM ammonium borate buffer pH 9.0 enabled the complete separation of the three couples of enantiomers in less than 30 min. The optimized CEC method was therefore validated and applied to the analysis of pharmaceutical formulation declared to contain only AML racemate.

Amlodipine besylate (AML) has become the most popular blood pressure medication for hypertensive pets. It belongs to the class I (high solubility and high permeability) according to BCS and is marketed in Europe only as white tablets equivalent to 2.5, 5.0 and 10.0 mg of amlodipine for oral administration. Unfortunately, oral AML dosage for cats and dogs is in the range 0.1–0.2 and 0.625–0.125 mg/kg/die respectively. Moreover, AML shows a slight solubility in water according to Ph. Eur. 7°. According to these considerations, the aim of this work was the complexation between soluble β-cyclodextrin polymer (CD) and AML using the solubilization/freeze-dried method to obtain powders easily dosable and soluble in water for the treatment of hypertension in pets. The complex in solution was evaluated by phase solubility studies that indicated the optimal 2:1 drug/CD ratio to form a stable complex. UV–Vis absorption and circular dichroism showed the formation of a complex with a weak bond such as confirmed by differential scanning calorimetry, infrared spectroscopy and fluorescence microscopy. In vitro dissolution/release tests were performed in water to investigate the influence of formulative parameters on drug dissolution/release properties. The inclusion of AML in CD increased its wettability, dissolution rate and solubility in water. This method could be a suitable approach for the administration of an extemporaneous solution of the antihypertensive drug to guarantee a correct dose to pets increasing the compliance

Cognitive dysfunctions are a common clinical feature of schizophrenia and represent important indicators of outcome among patients who are affected. Therefore, a randomized, controlled, monocentric, single-blind trial was carried out to compare two different rehabilitation strategies adopted for the restoration and recovery of cognitive functioning of residential patients with schizophrenia. A sample of 110 residential patients were selected and, during the experimental period, a group of 55 patients was treated with sets of domain-specific exercises (SRT+CRT), whereas an equal control group was treated with sets of non-domain-specific exercises (SRT+PBO) belonging to the Cogpack® software. The effects on the scores (between T0 and T1) of the variables treatment and time and of the interaction time X treatment were analyzed: for the total BACS, the main effect of the between-factors variable treatment is statistically significant (F=201.562 P=0.000), as well as the effect of the within-factors variable “time” (F=496.68 P=0.000).The interaction of these two factors is also statistically significant (F=299.594 P=0.000). The addition of cognitive remediation therapy (CRT) to a standard treatment of metacognitive training (MCT) resulted in a significant improvement in global neurocognitive functioning and has reported positive effects with regard to the strengthening of verbal and working memory, selective and sustained attention at T1. A relevant result is the statistically significance of “time X treatment” for all the tests administered: we can assume that the domain-specific cognitive training amplifies the effects of SRT, as the primary and secondary goals of the present study were achieved.