Evaluation of actarit/γ-cyclodextrin complex prepared by different methods
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This study used actarit (ACT), an antirheumatic drug, to examine the molecular interaction of ACT and γ-CD in a solid state as a result of cogrinding or freeze-drying and it assessed the dissolution of ACT. Differential scanning calorimetry revealed that coground ACT and γ-CD at molar ratios of 1:2 and 1:3 and freeze-dried ACT and γ-CD at molar ratios of 1:1 and 1:2 lacked an endothermic peak due to melting of ACT crystals. Thus, coground ACT and γ-CD at a molar ratio of 1:2 had molecular interaction, as did freeze-dried ACT and γ-CD at a molar ratio of 1:1. Powder x-ray diffraction revealed that coground and humidified ACT and γ-CD at a molar ratio of 1:2 produced a characteristic diffraction peak at 2θ = 15.2° and 16.5° due to the cage structure of γ-CD. In addition, freeze-dried ACT and γ-CD at a molar ratio of 1:1 that had been humidified produced a diffraction peak at 2θ = 6.0° and 15.9° characteristic of a hexagonal structure with head-to-head channels due to γ-CD. Assessment of dissolution revealed that ground mixtures (GMs) and freeze-dried mixtures had improved dissolution of ACT compared to ACT, ground ACT alone, and physical mixtures. The mechanism for this is presumably the result of molecular interaction in a solid state or molecular interaction in an aqueous solution. 1H–1H NOESY NMR spectra suggested that in a GM of ACT and γ-CD the benzene ring and methyl group of ACT partially enter the CD cavity. In addition, spectra for freeze-dried ACT and γ-CD suggested that protons of the methylene group of ACT and the benzene ring of ACT partially enter the CD cavity. These findings indicate that ACT and γ-CD inclusion complexes feature different forms of inclusion depending on how they are prepared, e.g., cogrinding or freeze-drying. Findings also indicated that selection of a method of preparation may play a major role in drug development.
KeywordsMolecular interaction Ground mixture Freeze dried γ-Cyclodextrin Actarit
The authors wish to thank Cyclo Chem Co. Ltd. for providing γ-CD. The authors also wish to sincerely thank Nippon Shinyaku Corporation for providing ACT.
- 2.Pankajkumar, S.Y., Kumar, V., Pratap, S.U., Bhat, R.H., Mazumder, B.: Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with PVP K30 and d-mannitol. Saudi. Pharm. J. 22, 77–84 (2013)Google Scholar
- 9.Dollo, G., Le, C.P., Chollet, M., Chevanne, F., Bertault, M., Burgot, J.L., Le, V.R.: Improvement in solubility and dissolution rate of 1,2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives. J. Pharm. Sci. 88, 889–895 (1999)CrossRefGoogle Scholar
- 13.Mangolim, C.S., Moriwaki, C., Nogueira, A.C., Sato, F., Baesso, M.L., Neto, A.M., Matioli, G.: Curcumin-β-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food. Chem. 153, 361–370 (2014)CrossRefGoogle Scholar
- 14.Iwata, M., Fukami, T., Kawashima, D., Sakai, M., Furuishi, T., Suzuki, T., Tomono, K., Ueda, H.: Effectiveness of mechanochemical treatment with cyclodextrins on increasing solubility of glimepiride. Pharmazie. 64, 390–394 (2009)Google Scholar
- 24.Toropainen, T., Heikkilä, T., Leppänen, J., Matilainen, L., Velaga, S., Jarho, P., Carlfors, J., Lehto, V.P., Järvinen, T., Järvinen, K.: Crystal structure changes of gamma-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide. Pharm. Res. 6, 1058–1066 (2007)CrossRefGoogle Scholar