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Abstract: The aim of our work was to develop a multicomponent inclusion complex of acetazolamide (ACZ) in order to investigate the combined effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) and triethanolamine (TEA) on the solubility of ACZ and its possibility of ophthalmic delivery. Phase solubility study was used to evaluate the complexation in solution at 25°C. Complex formation was also evaluated by comparing the infrared (FT-IR) spectra of the solid complexes with a simple physical mixture containing the same amount of ACZ. FT-IR experiments provided data indicating that the carbonamido group of ACZ is involved in the inclusion process. In vitro release data showed that both formulations, containing the freeze-dried ternary complex and the corresponding simple physical mixture of ACZ with HP-β-CD and TEA presented the fastest release rate of ACZ. These results suggest that the ACZ–HP-β-CD–TEA complex represents an effective novel formulation to enhance ACZ solubility in water, turning it promising for ophthalmic administration. [Copyright &y& Elsevier]

Abstract: The complex formation of chlorhexidine digluconate (CHX-G2) with hydroxypropyl-β-cyclodextrin (HPβCD) was studied using NMR spectroscopy. The results revealed that this surfactant agent shows an monomer/aggregate equilibrium, which is dependent on the concentration of this drug. This equilibrium can be modified by the presence of HPβCD, which reduces the aggregation of the CHX-G2 molecules. An inclusion process of the CHX-G2 aromatic residue within the cyclodextrin cavity was confirmed by 2D ROESY spectroscopy. 1H NMR titration studies of CHX-G2 with HPβCD in D2O confirmed the formation of higher order complexes between CHX-G2 and HPβCD. Moreover, the addition of HPβCD into CHX-G2 solutions forms insoluble aggregates. Such insoluble aggregates may result in the stacking of CHX-G2 molecules on the surface of the CHX-G2:HPβCD complexes. [Copyright &y& Elsevier]

Abstract: Here, we describe the chemical characterization of the inclusion complex between diclofenac (DCF) and methyl-β-cyclodextrin (M-β-CD) in the presence or absence of monoethanolamine (MEA). Several techniques were used to analyze the complex both in solution and in the solid state. Solubility of DCF was increased by the addition of M-β-CD. However, the DCF solubility increase was more significant by the addition of M-β-CD in the presence of MEA. In vitro permeation experiments through excised human skin revealed that DCF was enhanced by M-β-CD. Nevertheless, further improvement in the flux and the permeability coefficient of DCF was obtained by the ternary system DCF-M-ß-CD-MEA. [ABSTRACT FROM AUTHOR]

Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-β-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-β-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-β-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies. [ABSTRACT FROM AUTHOR]