Affiliations: National Institute for R&D of Isotopic and Molecular Technologies, Cluj-Napoca, Romania | “Terapia-Ranbaxy”, Cluj-Napoca, Romania | University of Oradea, Faculty of Medicine and Pharmacy, Oradea, Romania
Note: [] Corresponding author: I. Bratu, National Institute for R&D of Isotopic and Molecular Technologies, P.O. Box 700, RO-400293 Cluj-Napoca, Romania. Tel.: +40 264 584037; Fax: +40 264 420042; E-mail: [email protected].
Abstract: Solid state interactions of bioactive substance (4-cyclohexyl-1-[2-[(2-methyl-1-propanoyloxy-propoxy)-(4-phenylbutyl)phosphoryl]acetyl]-pyrrolidine-2-carboxylic acid, called Fosinopril), with β-cyclodextrin (β-CD), the so-called inclusion compounds of a bioactive (cardiovascular) drug is obtained by different preparation methods: kneading, co-precipitation and freeze-drying. The so obtained compounds were investigated by FTIR spectroscopy, X-ray diffraction method, and differential scanning calorimetric measurements (DSC) to evidence their formation. X-ray diffraction patterns show that the inclusion compound was obtained for kneaded, co-precipitation and freeze-dried products. The crystalline/amorphous degree for these compounds was also investigated. Molecular modeling (MM+ molecular mechanics) shows the spatial architecture of the inclusion compound in good agreement with FTIR experimental data: the drug is included with the propanoyloxy-propoxy group inside β-cyclodextrin cavity. These findings may constitute a direct contribution to the molecular encapsulation of Fosinopril into β-cyclodextrin, improving Fosinopril stability and bioavailability of the drug, also.
