Inclusion of Anesthetics in Cyclodextrins: Structural Investigation of Solid Inclusion Complexes of Butamben

Abstract

Single crystal and powder X-ray diffraction techniques were used to characterize inclusion complexes formed between the local anesthetic butamben (4-aminobenzoic acid butyl ester) and various cyclodextrins (CDs). Kneading butamben with the native hosts β- and γ-CD yielded microcrystalline products, unequivocally identified as inclusion complexes by powder X-ray diffraction. Single crystals of a 1:1 inclusion complex between butamben and permethylated β-CD (TRIMEB) were isolated. X-ray analysis revealed that the guest is included with the ester moiety fully encapsulated in the TRIMEB cavity. However, a major part of the phenylamine residue protrudes from the host primary side, entering the secondary side of a translated TRIMEB molecule to which it hydrogen bonds, both directly [–NH^A ⃛O(host)] and indirectly [–NH^B ⃛O(water) ⃛O(host)]. This unusual mode of guest inclusion is associated with a novel channel-like complex packing arrangement in the monoclinic space group P2¹. The included drug molecule adopts a more extended conformation than that found in the crystal of butamben, whose X-ray structure was also determined in this study.

Acknowledgements

We thank the University of Cape Town and the NRF (Pretoria) for financial assistance. This material is based upon work supported by the National Research Foundation under Grant number NRF 2053361. Any opinions, findings and conclusions or recommendations expressed in the material are those of the author and do not necessarily reflect the views of the National Research Foundation.