Nuclear Magnetic Resonance Investigation of the Stoichiometrics in β-Cyclodextrin:Steroid Inclusion Complexes

Djedaïni, Florence; Perly, Bruno

doi:10.1002/jps.2600801213

Cited by 54 publications

(26 citation statements)

References 7 publications

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“…21,22) In contrast, NMR studies allow a clear distinction between inclusion and other possible external interaction processes. This technique provides the most evidence for the inclusion of a guest into the hydrophobic CD cavity in solution.…”

Section: Resultsmentioning

confidence: 99%

Molecular Modelling and 1H-NMR: Ultimate Tools for the Investigation of Tolbutamide: .BETA.-Cyclodextrin and Tolbutamide: Hydroxypropyl-.BETA.-Cyclodextrin Complexes.

Veiga

Fernandes

Carvalho

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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Cyclodextrins (CDs) are cyclic oligosaccharides composed of ␣-1,4-linked D-glucopyranose units. The most common of these ring-shaped molecules are the a-, b-, and g-CDs formed by six, seven, and eight glucose units, respectively. 1)CDs are toroidal molecules with a truncated cone structure where the secondary hydroxyl groups are located on the wider side of the ring, while the primary hydroxyl groups are positioned on the opposite, narrower side of the torus. The -CH groups carrying the H-1, H-2, and H-4 protons are located on the exterior of the molecule and the hydroxyl groups are oriented to the cone exterior, which makes the external faces of CDs decidedly hydrophilic. The interior of the torus, which offers an environment of much lower polarity than that present in water, is lined by two rings of -CH groups (H-3 and H-5) and by a ring of glycosidic "ether oxygens" (O-4), with H-6 located near the cavity.2) A great variety of "guest" molecules of suitable size and shape may be entirely or partially included in this hydrophobic cavity, resulting in a stable association without formation of covalent bonds. The complexation driving forces have been attributed to hydrophobic interactions, van der Waals-London dispersion forces, and hydrogen bonds. 3,4) In the pharmaceutical field this complexation phenomenon has been extensively applied to enhance the solubility, dissolution rate, and bioavailability of sparingly soluble drugs in gastrointestinal fluids.5-10) Because of the increasing interest in CDs and their inherent usefulness, several studies have been conducted to clarify the mechanism of complexation.In previous studies, the ability of b-CD and hydroxypropyl-b-cyclodextrin (HP-b-CD) to form inclusion complexes with tolbutamide (TBM), in order to increase its solubility, dissolution rate, 11) and oral bioavailability 12) was evaluated. Important information on the solid-phase structure of these complexes may be obtained via X-ray analysis when a suitable crystal of the product is available. However, X-ray diffractograms of the lyophilized TBM:CD complexes previously reported 11) have demonstrated the complete amorphousness of the product obtained, making it impossible to gain more detailed information from them. Although solubility studies indicated the existence of complexation between TBM and b-CD or HP-b-CD in solution, 11) the exact mechanism of complexation could not be deduced.The use of computer-aided molecular modelling and 1 H-NMR studies has proved to hold promise for such purposes, especially for systems or molecules of biological interest which "act" in aqueous medium. These techniques have been used as important tools for investigating the conformation of the most favored complexes and to obtain a better knowledge of the geometry of the system and the topology of the interactions between guest and CDs. [13][14][15][16][17] Therefore in the present study we coupled these techniques, which allowed us to compare and to integrate the theoretical findings obtained in a vacuum (molecular modelling) ...

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Section: Resultsmentioning

confidence: 99%

Molecular Modelling and 1H-NMR: Ultimate Tools for the Investigation of Tolbutamide: .BETA.-Cyclodextrin and Tolbutamide: Hydroxypropyl-.BETA.-Cyclodextrin Complexes.

Veiga

Fernandes

Carvalho

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…On the other hand, protons located on the outside experience very little or no effect. [21][22][23][24] Table 1 details the shifts observed for the internal proton H-5, suggesting that the drug has entered the cyclodextrin cavity to form an inclusion complex. There are no shifts for external protons, indicating that the complex formed can be classified as an inclusion complex.…”

Section: Characterization Of Inclusion Complexmentioning

confidence: 99%

Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole: β-cyclodextrin complex

et al. 2006

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The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex with 1:1 molar ratio with β-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including 1 H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k 1:1 ). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with β-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug: cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole:β-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values.

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“…Several medicinal substances have been successfully complexed by CD, such as antineoplastic agents [8,[21][22][23][24]. These complexes can increase the stability and improve the solubility and bioavailability of the substance and modify the pharmacokinetics of the resulting drugs with a subsequent reduction in adverse effects [6,[13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…A considerable literature was devoted to b-CD and its applications especially in the pharmacological area [6,[13][14][15][16][17][18][19][20]. Several medicinal substances have been successfully complexed by CD, such as antineoplastic agents [8,[21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Effects of solvent, pH and β-cyclodextrin on the fluorescent behaviour of lomustine

Fisli

Bensouilah

Dhaoui

et al. 2011

J Incl Phenom Macrocycl Chem

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Fluorescent behaviour of lomustine, a DNA cross-linking agent, was investigated in different solvents, pH and in the presence of b-cyclodextrin (b-CD). The solvents in which fluorescence spectra were observed play a major role in determining the spectral intensity of fluorophore, since it was found to exhibit new fluorescent properties essentially influenced by intermolecular interactions, particularly by intermolecular H-bonding formed with solvents. The pH-dependence profile was typically U-shape with a maximum at pH between 3.51 and 6.58. It was corroborated that the fluorescence emission band of lomustine is significantly intensified in the presence of b-CD. From the changes in the fluorescence spectra, it was concluded that b-CD forms a 1:1 inclusion complex with lomustine and its association constant was calculated.

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Nuclear Magnetic Resonance Investigation of the Stoichiometrics in β-Cyclodextrin:Steroid Inclusion Complexes

Cited by 54 publications

References 7 publications

Molecular Modelling and 1H-NMR: Ultimate Tools for the Investigation of Tolbutamide: .BETA.-Cyclodextrin and Tolbutamide: Hydroxypropyl-.BETA.-Cyclodextrin Complexes.

Molecular Modelling and 1H-NMR: Ultimate Tools for the Investigation of Tolbutamide: .BETA.-Cyclodextrin and Tolbutamide: Hydroxypropyl-.BETA.-Cyclodextrin Complexes.

Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole: β-cyclodextrin complex

Effects of solvent, pH and β-cyclodextrin on the fluorescent behaviour of lomustine

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