Cyclodextrin complexation of NSAIDSs: physicochemical characteristics

Loftsson, Þorsteinn; Ólafsdóttir, Birna J.; Fridriksdóttir, H; Jónsdóttir, Sigríður

doi:10.1016/0928-0987(93)90023-4

Cited by 100 publications

(44 citation statements)

References 16 publications

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“…These differences can be large, for example with a-cyclodextrin at 25 "C the equilibrium constant is 722 for neutral benzoic acid, but only 11 for the benzoate anion [33]. For ibuprofen (pK, 5.2) and hydroxypropyl P-cyclodextrin the following data were obtained [34]: pH 4.6, 1740; pH 5.6, 1200; pH 6.24, 210, and pH 7.54, 50.…”

Section: The Modelmentioning

confidence: 98%

A theoretical approach to chiral capillary electrophoresis with some practical implications

1994

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A theoretical approach to chiral capillary electrophoresis with some practical implications ZENECA Pharmaceuticals, Hurdsfield, Macclesfield, Cheshi, A simple model has been proposed which explains enantiomeric resolution in capillary electrophoresis in terms of differential interactions with a chiral selector and differential migration of the two enantiomer-chiral selector complexes. The equations derived allow predictions to be made and there is good support for the model in literature data.

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Section: The Modelmentioning

confidence: 98%

A theoretical approach to chiral capillary electrophoresis with some practical implications

1994

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“…The large upfield shift of protons H-3 and H-5, with nearly to central location inside the b-CD cavity, can only be explained by assuming that the aromatic benzene ring of the TBM molecule is located inside the cavity. 13) The fact that H-3 and H-5 protons have a stronger shift than the H-6 protons, which are located on the cavity rim at the narrow end of the CD molecule, indicates that during complex formation the TBM molecule enters the b-CD cavity from the more accessible wider side.…”

Section: )mentioning

confidence: 99%

“…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) with the experimental data ( 1 H-NMR) to gain insight into the mode of inclusion and to clarify the most probable conformation of the TBM : CD complexes in aqueous medium. …”

mentioning

confidence: 99%

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

et al. 2001

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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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“…In aqueous solution, the apolar CD cavity is occupied by water molecules which are energetically unstable, and therefore can be substituted by appropriate guest molecules, forming inclusion complexes [14][15][16]. The experimental methodology for the evaluation of the inclusion complexation of amphiphilic drugs with CDs includes the determination of association equilibrium constants for the inclusion process [17,18].…”

Section: карактеризација на инклузиони комплекси меѓу бифоназол и разmentioning

confidence: 99%

Characterisation of Inclusion Complexes Between Bifonazole and Different Cyclodextrins in Solid and Solution State

Kelemen

Csillag

Hancu

et al. 2017

Maced. J. Chem. Chem. Eng.

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The aim of this study is to confirm the formation of inclusion complexes between bifonazole (BFZ) and different cyclodextrin (CD) derivatives. BFZ, an imidazole antifungal derivative, is a very hydrophobic compound, which is a major drawback in obtaining topical pharmaceutical formulations with optimal bioavailability. CDs may increase local drug delivery by enhancing the drug release and/or permeation. Several native and derivatized CD derivatives were tested in the experiments. The binary systems between BFZ and CDs were prepared in two molar ratios by physical mixing methods. The physicochemical properties of these complexes were studied by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy methods. The results showed favorable molecular interaction between the components in solid state and in solution. 1 H NMR-CD titrations and molecular modeling study showed that the most stable complex was obtained when using γ-CD. The Job's method and 2D NMR spectroscopy support the 2 : 1 stoichiometry of the BFZ : γ-CD complex.Keywords: bifonazole; cyclodextrins; differential scanning calorimetry; Fourier transform infrared spectroscopy; H NMR-CD titrations КАРАКТЕРИЗАЦИЈА НА ИНКЛУЗИОНИ КОМПЛЕКСИ МЕЃУ БИФОНАЗОЛ И РАЗЛИЧНИ ЦИКЛОДЕКСТРИНИ ВО ЦВРСТА СОСТОЈБА И ВО РАСТВОРЦелта на ова истражување е да се потврди образувањето на инклузиони комплекси меѓу бифоназол (BFZ) и различни циклодекстрински (CD) деривати. BFZ, кој претставува имидазолски фунгициден дериват, е силно хидрофобно соединение, што претставува голем недостаток при добивање топични фармацевтски препарати со оптимална биорасположливост. CD може да ја зголеми локалната испорака на лекот со подобрување на ослободувањето и/или пропустливоста на лекот. Експериментално беа тестирани неколку нативни и дериватизирани CD. Бинарните системи меѓу BFZ и CD беа подготвени во два моларни односа со методи на физичко мешање. Физичкохемиските својства на овие комплекси беа испитувани со диференцијална скенирачка калориметрија (DSC), Фуриеова трансформна инфрацрвена (FTIR) спектроскопија и со нуклеарно-магнетни резонантни спектроскопски методи. Резултатите покажуваат позитивна молекулска интеракција меѓу компонентите во цврста фаза и во раствор. Титрациите на 1 H NMR-CD и испитувањето со молекулско моделирање покажуваат дека најстабилен комплекс се добива со

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Cyclodextrin complexation of NSAIDSs: physicochemical characteristics

Cited by 100 publications

References 16 publications

A theoretical approach to chiral capillary electrophoresis with some practical implications

A theoretical approach to chiral capillary electrophoresis with some practical implications

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

Characterisation of Inclusion Complexes Between Bifonazole and Different Cyclodextrins in Solid and Solution State

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