Study of the stability and structure of molecular inclusion complexes of myristic acid in cyclodextrins

DOS SANTOS, CRISTINA; VILLAGRÁN DOS SANTOS, NICOLÁS; SANTAGAPITA, PATRICIO R.; PERULLINI, M; MARINO, CARLA; MAZZOBRE, M. FLORENCIA; BUERA, M. PILAR

CABA

Simposio; Exploring the Frontiers of Chemistry: Challenges for the 21st Century.; 2019

β-Cyclodextrin (BCD) and 2-hydroxypropyl-β-cyclodextrin (HBCD) are cyclic oligosaccharides capable of encapsulating non-polar bioactive compounds, increasing their aqueous solubility and changing their physicochemical properties. The objective of this work was to study the encapsulation of myristic acid (MYR) in BCD and HBCD by changing ligand-cyclodextrin (L-CD) molar ratio and stirring time. Inclusion complexes were prepared by coprecipitation and lyophilization. The stability of the complexes was studied storing the samples for 60 days at different relative humidities (RH). Encapsulation and ligand-CD supramolecular interactions were confirmed by a multianalytical approach using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), small angle X-ray scattering (SAXS) and 1H-NMR spectroscopy. The thermograms of the dried systems confirmed that the MYR was partially encapsulated (40- 70%) in both cyclodextrins (CD). The encapsulation was maximized by increasing the CD proportion on the MYR-CD molar ratio and by stirring 7 hours at 25° C. After 60 days of storage at 85-95% RH, a complete encapsulation of the ligand was achieved for 1:3 MYR-BCD molar ratio. This ratio showed also the maximum modifications of the chemical shifts of the H-3 and H-5 protons of the BCD analyzed by the method of continuous variations (Job) in 1H-NMR and by the complete disappearance of the MYR scattering peaks after HPBCD complexation in SAXS curves. The presence of MYR modified the water sorption isotherms of BCD and HBCD, being the amount of adsorbed water smaller in the complexes than in both cyclodextrins. The fractal contour dimension of the particles (Df) and the spectral distribution (FFT) were analyzed by the box count method from SEM images, revealing differences in the morphology and surface texture of all the studied systems. Finally, the presence of MYR decreased the glass transition temperatures of the HBCD at all the HR tested. The multianalytical approach allowed to conclude that the stoichiometry of the MYR-CD complexes is 1: 3, being their formation of non-covalent nature. MYR inclusion is favored in high humidity environments and involves the displacement of water molecules from the inner cavity of the CD. These data are useful for selecting storage conditions or predicting the shelf life of dehydrated food ingredients or pharmaceutical products formulated with bioactive compounds encapsulated in cyclodextrins.