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

Abstract

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

Supramolecular self-assembly with p-coumaric acid offers the first cocrystal for perfecting the physicochemical peculiarity and enhancing the antifungal effect of drug bifonazole

“…S1 †. Comparing the IR spectra between raw material BFZ and cocrystal BFZ–TPA, it is readily found that the stretching vibration of ν (CN) in BFZ is situated at 1644 cm −1 , 18 while this peak is shifted to 1604 cm −1 in cocrystal BFZ–TPA, indicating that the CN group of the BFZ molecule forms a novel interplay with TPA. Furthermore, the IR spectrum of the TPA molecule reveals two characteristic peaks at 1674 cm −1 and 3378 cm −1 , corresponding to the absorption peaks of stretching vibration for the ν (CO) and ν (O–H) in the carboxylic acid group.…”

“…16 In response to the above issues, many pharmaceutical methods have been utilized to make up for these deficiencies of BFZ, such as hydrophilic multiple emulsion, nano-emulsion, microemulsion-based hydrogel, in situ oral topical gel, cyclodextrin, and so on. 15,[17][18][19] Definitely, a large quantity of related measures involving extensive chemical modification of BFZ have also been taken. 20,21 Although these approaches have already been fruitful to a certain extent, they are also subject to great difficulties including the complicated operations and steep costs in dosage form design, as well as the massive side products or impurities arising from the synthetic process.…”

Formulation and Evaluation of Timolol Maleate Proniosomal Gel for Ocular Drug Delivery

“…Partition coefficient, PC = Co/Ca Where, Co is the concentration of Timolol maleate in octanol, and Ca is the concentration of the Timolol maleate in aqueous phase. 8 Compatibility studies using FTIR The unique absorption peaks for C=C stretching non-conjugated at 1650.73 cm -1 , N-H bending at 1581.09 cm -1 , and N-H bending at 1581.09 cm -1 were discovered in the FTIR spectra of Timolol maleate. At 1218.35 cm -1 , -H 2 C-NH-Amines stretch, -CH 2 -O-R-Ethers at 1315.07 cm -1 , and C-H bend aromatic at 920.05 cm -1 .…”

Characterization of Inclusion Complexes between Miconazole and Different Cyclodextrin Derivatives

“…An indication of the host-guest molecular interaction, provided by DSC analysis, is the disappearance of the melting endotherm of the guest in the DSC thermogram of the binary system, as well as the shifting of the melting peak of the guest. The melting enthalpy is an indication of the amount of guest not involved in the interaction with the CD [13][14][15][16][17].…”