17-β-Estradiol—β-Cyclodextrin Complex as Solid: Synthesis, Structural and Physicochemical Characterization

Abstract

17-β-estradiol (EST) is the most potent form of naturally occurring estrogens; therefore, it has found a wide pharmaceutical application. The major problem associated with the use of EST is its very low water solubility, resulting in poor oral bioavailability. To overcome this drawback, a complexation with cyclodextrins (CD) has been suggested as a solution. In this work, the host–guest inclusion complex between the ß-CD and EST has been prepared using four different methods. The obtained samples have been deeply characterized using 13C CP MAS solid state NMR, PXRD, FT-IR, TGA, DSC, and SEM. Using SCXRD, the crystal structure of the complex has been determined, being to the best of our knowledge the first solved crystal structure of an estrogen/CD complex. The periodic DFT calculations of NMR properties using GIPAW were found to be particularly helpful in the analysis of disorder in the solid state and interpretation of experimental NMR results. This work highlights the importance of a combined ssNMR/SCXRD approach to studying the structure of the inclusion complexes formed by cyclodextrins.

Synthesis and Inclusion Properties of a β-Cyclodextrin Heptaphosphoramidate

“…This suggests that the Dex-P ( 7 ) guest molecule might predominantly reside near the lower part of the cavity of β-CD heptaphosphoramidate ( 4 ). This can be explained by the well-known fact that β-CD hosts typically form a 2:1 inclusion complex with a steroid molecule, as demonstrated by the crystal structure between cholesterol and native β-CD [ 40 ] and another study [ 41 ].…”

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin

“…The structural differences among the synthesized complexes were studied using 13 C CPMAS ssNMR analysis, showing differences in shape and signal intensity [64]. The most significant change between the ligand (DiMeOC) and its magnesium metal complex (DiMeOC-Mg) resides in the region of the carbonyl groups; for DiMeOC (ligand), two different carbonyl groups are observed at 185 ppm and 189 ppm (see Figure 4).…”

Solid Forms and β-Cyclodextrin Complexation of Oxymetholone and Crystal Structure of Metribolone

“…Some diffraction lines of the pure steroid and for the oxymetholone-beta-cyclodextrin complex appear by random coincidence at similar 2ϴ, but still they are slightly shifted, which suggests that the inclusion of the steroid, which is a small molecule, is easily fitted inside the cyclodextrin cavity. Some preparations of beta-cyclodextrin with other steroidal compounds such as methyltestosterone [38], estradiol [39], and progesterone [40] have been recently reported.…”