We have measured the interfacial tension (γ) between H2O and CO2 with a drop tensiometer that permitted us to regulate the drop area and to perform elasticity measurements. We observed that γ decreased with time and with the CO2 pressure. We first analyzed the adsorption of CO2 onto surface water by plotting the initial interfacial tension (γ0) versus CO2 fugacity and applied Gibbs and then Langmuir-Freundlich equations. We have calculated the interfacial area occupied by CO2 molecules onto H2O as well as the equilibrium constant and the thermodynamics parameters of adsorption. This permitted us to understand that the CO2 was adsorbed onto the surface water by formation of a one-to-one H-type complex with H2O. Second, we attributed the kinetics phenomena to the formation of interfacial clusters between water and CO2, which gave interfacial quasi-crystalline structure as shown by compression of the drop area at the end of the adsorption kinetics. We studied this interfacial organization by measuring the apparent elasticity versus time and CO2 pressure. This measurement allowed us to propose an interfacial organization based on the formation of small blocks, which grow to fill the interface, as already observed by Teng and al. Then we determined the filling of the clusters cavities by analyzing the difference between γ0 and γeq (Δγ) by means of the Hill equation. This permitted us to determine that this filling depended on temperature and was cooperative.

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Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated rifampicin-CD complexes in terms of rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between rifampicin and methylated beta-cyclodextrin (RAMEB) or hydroxypropyl-beta-cyclodextrin (HPbetaCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an A(L)-type curve for RAMEB and a B(S)-type for HPbetaCD. Stability constants calculated for a 1:1 molar ratio of CD/rifampicin were 73.4 +/- 8.2 M(-1) for RAMEB and 68.5 +/- 5.2 M(-1) for HPbetaCD. Complexes with RAMEB or HPbetaCD increased 22 times and 7.6 times respectively the apparent solubility of rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPbetaCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPbetaCD complexes measured by the total rifampicin MIC against A. baumannii was similar or lower to free rifampicin MIC respectively. Complexation did not alter the rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active rifampicin and optimize its lung pharmacokinetic profile.