Succinyl-β-cyclodextrin: Influence of the substitution degree on albendazole inclusion complexes probed by NMR

Abstract

Succinyl-β-CD derivatives were obtained by green synthesis with degrees of substitution (DS) 1.3 and 2.9. The spray-drying technique was used to obtain albendazole (ABZ):succinyl-β-CD inclusion complexes. Phase solubility diagrams indicated that both succinyl-β-CD derivatives formed 1:1 molar ratio ABZ complexes, but the complex with DS 2.9 has a lower formation constant. The presence of stable inclusion complexes in aqueous solution was confirmed by NMR. For both complexes the aromatic moiety is encapsulated into the host cavity. In the solid-state, C andN NMR spectral differences between ABZ and ABZ included in spray-dried systems showed that strong structural changes occurred in the systems. At least two different ABZ amorphous species were identified based on DS. ABZ species were stable over more than six months based on spectral data. Finally, the influence of DS in the number and type of the inclusion complexes was elucidated.

A Review of Applications of Solid-State Nuclear Magnetic Resonance (ssNMR) for the Analysis of Cyclodextrin-Including Systems

“…In most of the cases, ssNMR is used to prove the complexation, characterize the structure of a formed complex, and find a possible reason for its stability. However, as the usage of CDs serves to enhance the solubility, hence, bioavailability, of medical substances in solid-state forms of medication, a common reason for ssNMR experiments is either differentiation between amorphous and crystalline complex forms [ 22 , 23 ] or comparison of different complexation methods. The examples are the following complexes: CD-bisacodyl, where co-crystallization and co-evaporation have been compared [ 29 ], or CD-hydroxytyrosol, where comparison for physical mixing, spray-draying, and freeze-drying methods has been conducted [ 53 ].…”

“…Another interesting example of the application of ssNMR was the study of the albendazole:succinyl-β-CD inclusion complexes in spray-dried samples [ 22 ]. Albendazole itself was found to exist in a few tautomeric forms, depending on its crystal structure.…”

The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole

“…Forms I and II are enantiomerically related forms [12], and the commercially available form I is metastable at room temperature while form II is stable. Therefore, complexation with cyclodextrins can not only increase solubility, but also stabilize the compounds [13].…”

“…Forms I and II are enantiomerically related forms [12], and the commercially available form I is metastable at room temperature while form II is stable. Therefore, complexation with cyclodextrins can not only increase solubility, but also stabilize the compounds [13]. A β-Cyclodextrin inclusion complex has been reported to stabilize albendazole and, consequently, improve its water solubility and dissolution rate.…”

Structural Characterization of a Cyclodextrin/l-menthol Inclusion Complex in the Solid-state by Solid-state NMR and Vibrational Circular Dichroism

“…[25][26][27][28] The 13 C solid-state NMR technique using magic angle spinning (MAS) with a wide resonance range (0 -220 ppm) can discriminate between the signals of CyD (host) and incorporated molecule (guest) in the solid state. [28][29][30][31][32][33] In addition, chemical shifts are used to investigate the strength of hydrogen bonds and secondary structure on the basis of bond dihedral angles.…”