Impact of Chlorpromazine Self-Association on Its Apparent Binding Constants With Cyclodextrins: Effect of SBE7-β-CD on the Disposition of Chlorpromazine in the Rat

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

“…Whereas the MIC of control non-irradiated CPZ was 60 µg/mL, that of the 24 hrs irradiated CPZ was 3.75 µg/mL. These results confirmed previous observations that indeed, irradiation yielded a product that was far more (8 fold) active against the test organism than CPZ [24]. Nevertheless, as is the case with CPZ, activity of the 24 hrs irradiated sample is bacteriostatic at the concentrations employed (maximum of 20 mg/mL).…”

“…But this concentration is lower with one or more orders of magnitude than the concentration at which polymerizations takes place [39], so that we may consider that CPZ monomers absorb, in the initial solution, the laser radiation. This is in agreement with the proposal made in [40] that self-association of phenothiazines, (in particular CPZ), is a sequential process of adding monomeric units as concentration increases, rather than micellisation according to the pseudophase separation model. On the other hand, the CPZ molar concentration used in our experiments was around 5.6×10 −2 M (20 mg/mL) and the literature reports [40], [41] display a large range of cmc values: 2.2×10 −2 M to 0.05×10 −3 M (measured at pH 7.0); the same broad display of values is shown for PZ which at 20 mg/mL has molar concentration of around 6.2×10 −2 M and the cmc according to [41] is 3.6×10 −2 M. More, surface tension measurements made on CPZ show a value for cmc around 10 mg/ml [41].…”

“…Starting from the fact that CPZ is known to self-associate, the self-association and cyclodextrin binding properties of CPZ have been studied via fluorescence and UV-VIS absorption measurements and the effect on pharmacokinetic parameters in rats when dosed with a SBE(7)-beta-CD containing formulation was evaluated [24]. It was found that the SBE(7)-beta-CD binding constant of CPZ is strongly depending on concentration and the variation can be attributed to the self-association of CPZ.…”

Novel 1-indanone Thiosemicarbazone Antiviral Candidates: Aqueous Solubilization and Physical Stabilization by Means of Cyclodextrins

“…Two types of complexes can coexist: (i) inclusion and (ii) non-inclusion complexes (24,25). The CD complexation of these drugs may also prevent their self-aggregation into a crystal lattice and their precipitation (9,26,27). On the other hand, native and chemically modified CDs display an intrinsic selfassembly tendency in water that leads to the generation of physically stable nano-aggregates (28).…”

Preclinical comparison of intravenous melphalan pharmacokinetics administered in formulations containing either (SBE)7 m‐β‐cyclodextrin or a co‐solvent system

“…Other reports in the literature have shown that modified cyclodextrins present within intravenous drug formulations have the potential to alter drug plasma concentration versus time profiles [3] or contribute to increased renal drug elimination [4][5][6]. Our group has been investigating scenarios in which interactions between drug molecules and cyclodextrins may impact upon therapeutic activity or drug pharmacokinetic properties.…”