Investigation of Tenoxicam and γ-Cyclodextrin Binary and Ternary Complexes

Tenoxicam is a widely used non-steroidal anti-inflammatory drug (NSAID). Itscomplexation with cyclodextrin was studied in order to improve its aqueoussolubility and to decrease its side-effects. Two- and three-component systems inseveral mole-ratios were prepared by means of two different methods. The drugliberation profile, the in vitro membrane diffusion and the n-octanol/water partitioncoefficient were investigated. The presence of complexes was detected via thermoanalyticaland X-ray diffractometric studies. On the basis of these data, several compositionswere selected for incorporation into topical dosage forms.     

Preparation and investigation of mixtures containing lidocaine base and β-cyclodextrin

The effects of β-cyclodextrin (β-CD) on the solubility properties of lidocaine base were studied. Products were prepared by physical mixing, kneading, spray-drying and precipitation methods in drug : β-CD ratios of 3:1, 2:1, 1:1, 1:2 and 1:3. Some auxiliary materials (hydroxy acids, etc.) were also used. The solubility and the rate of dissolution both in distilled water and in artificial gastric juice, the in vitro diffusion, the thermoanalytical properties (TG, DTG, DSC and DTA) and the surface tension were determined, and the measured results were compared with the corresponding data for lidocaine hydrochloride.     

Freeze-Dried Complexes of Furosemide with β-Cyclodextrin Derivatives

A freeze-drying method was used to prepare complexes of furosemide (guest) with three derivatives of -cyclodextrin (hosts) in different molecular ratios in order to increase the aqueous solubility and rate of dissolution of the drug, and also to study the influence of this method on different parameters of the guest and the host, such as the diffusion rate constant and the partition coefficient, and additionally the surface tension activity of the host (if any). The hosts were found to have significant, increasing effects on the solubility and the rate of dissolution of furosemide. X-ray diffraction confirmed the host–guest interaction, in support of the earlier results. The freeze-drying method increased the diffusion rate of the drug in complex form, while the partition coefficient varied with the type of -cyclodextrin in the product. It is well known that CD derivatives are highly surface active which gives rise to their hemolytic action. Our observations showed that their presence with furosemide in complex form might decrease (if not diminish) the hemolytic action.     

Thermoanalytical Studies on Complexes of Furosemide with β-Cyclodextrin Derivatives

Solid formulas obtained between furosemide and two β-cyclodextrin derivatives (HP-β-CD and RAMEB) were prepared by different methods and in various ratios (1:1 and 1:2). The inclusion complex formation between the drug and the β-CDs of 1:1 ratio was evaluated by mean of thermal analysis (DSC, TG and EGD). Supplementary techniques, such as X-ray diffraction, were also applied to interpret the results of the thermal study of physically mixed and kneaded products. Both studies demonstrated the formation of inclusion complexes in all samples except the physical mix samples; formation of true inclusion complexes was then possible only when the components were in melted form. The complexation increased the solubility and the rate of dissolution of the drug. RAMEB was found to be a better complexing agent than HP-β-CD; in both ratios it can be selected as a vehicle in furosemide tablet preparations. This revised version was published online in August 2006 with corrections to the Cover Date.     

Effect of Cyclodextrins on the Biofilm Formation Capacity of Pseudomonas aeruginosa PAO1

Quorum sensing (QS) is a population-density-dependent communication process of microorganisms to coordinate their activities by producing and detecting low-molecular-weight signal molecules. In pathogenic bacteria, the property controlled by QS is often related to infectivity, e.g., biofilm formation. Molecular encapsulation of the QS signals is an innovative method to prevent the signals binding to the receptors and to attenuate QS. Cyclodextrins (CDs) may form an inclusion complex with the signals, thus reducing the communication (quorum quenching, QQ). A systematic study was performed with α-, β-cyclodextrin, and their random methylated, quaternary amino and polymer derivatives to evaluate and compare their effects on the biofilm formation of Pseudomonas aeruginosa. To examine the concentration-, temperature- and time-dependency of the QQ effect, the CDs were applied at a 0.1–12.5 mM concentration range, and biofilm formation was studied after 6, 24, 48 and 72 h at 22 and 30 °C. According to the results, the QS mechanism was significantly inhibited; the size of the cavity, the structure of the substituents, as well as the monomeric or polymeric character together with the concentration of the CDs have been identified as key influencing factors of biofilm formation. Statistically determined effective concentration values demonstrated outstanding efficiency (higher than 80% inhibition) of α-CD and its random methylated and polymer derivatives both on the short and long term. In summary, the potential value of CDs as inhibitors of QS should be considered since the inhibition of biofilm formation could significantly impact human health and the environment.     

Release of cationic drugs from loaded clay minerals

The adsorption of promethazine chloride [10-(2-dimethylammonium propyl) fenothiazine chloride] and buformin hydrochloride (1-butylbiguanidine chloride) on montmorillonite was studied in previous work. The present article focuses on the desorption of these molecules from their organocomplexes in a medium of artificial intestinal juice (pH 7.0 ± 0.1) at the temperature of the human body (37 ± 0.5 °C). The desorption was investigated by kinetic studies, basal spacing measurements and Fourier transform IR studies. Important quantitative differences were observed: buformin, which adsorbed in a monolayer coverage, exhibited a very high desorption rate, whereas promethazine formed a pseudotrilayer arrangement and showed a lower dissolution rate. Received: 20 January 2001 Accepted: 8 March 2001