Astemizole/Cyclodextrin Inclusion Complexes: Phase Solubility, Physicochemical Characterization and Molecular Modeling Studies (original) (raw)

Received 5 May 2008; accepted 20 August 2008; published online 31 October 2008 Abstract. The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MβCD) and 2- ...

The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MβCD) and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) in aqueous solution by phase solubility studies. Inclusion complexes with MβCD in the solid state were then prepared by different methods, i.e., kneading, coevaporation (COE), spray-drying (SD), and lyophilization (LPh). The physicochemical properties of these complexes were subsequently studied by means of differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction techniques. Phase solubility diagrams with MβCD and HPβCD were classified as AP type, indicating the formation of 1:1 and 1:2 stoichiometric inclusion complexes. The apparent stability constants (KS) calculated from the phase solubility diagram were 145.69 M−1 (K 1:1) and 11.11 M−1 (K 1:2) for MβCD and 126.94 M−1 (K 1:1) and 2.20 M−1 (K 1:2...

Abstract. The interaction in solution between 2,4-dichlorophenoxyacetic acid with α- and β-cyclodextrins was evaluated by phase solubility studies. Association constants were calculated by this technique. The stoichiometries were 1: 2 and 1: 1 for the α- and β-cyclodextrin complexes, respectively. In order to corroborate the complexation and the knowledge of structural aspects of the host: guest interaction, proton nuclear magnetic resonance (1H-NMR) spectroscopy was employed. The application of the continuous variation technique corroborated the calculated complex stoi-chiometries by solubility assays. Complementary NOE studies were applied in order to corroborate the proposed complex structures. Key words: solubility, 1H-NMR, stoichiometry, cyclodextrins 1.

Purpose: The present study is aimed to study the host-guest inclusion complexation of the naturally occurring cyclodextrins (CDs), namely; (-CD,-CD, and -CD) with mitiglinide (MIT). Methods: Host-guest inclusion complexation was simulated using semi-empirical PM3 method. Results: The obtained results clearly indicate that the complexes formed are energetically favored in the presence of γ-CD (E comp = -17.884 kcal/mol) of the optimal configurations of (1:1) MIT/γ-CD inclusion complexes. Moreover, the results obtained reveal that the formation of more stable MIT/γ-CD complex compared to MIT/-CD or MIT/-CD complexes is primarily due to differences in intermolecular hydrogen bonding. Conclusion: The present theoretical results may be informative to scientists who are devoting themselves to developing effective methods for enhancing the drug solubility.

Equilibrium constants and standard molar enthalpies of reaction were determined by titration calorimetry for the reaction of 1-butanol with 2-hydroxypropyl-b-cyclodextrin (HP-b-CD) in aqueous solution at different concentrations of NaCl (0-1.9 M). The standard molar free energy and entropy changes associated to the complexation were calculated from the corresponding equilibrium constants, K, and standard enthalpies determined experimentally. In NaCl solutions the inclusion complexes ButOH/HP-b-CD are more stable than in water and their stability increases at increasing NaCl concentration; otherwise, the standard molar enthalpy associated to the formation of the complexes does not change with the increasing of salt concentration. The dependence of K on NaCl concentration were used to evaluate the number of water molecules displaced from the hydration shells of HP-b-CD and ButOH in forming complexes.