NMR studies of Sugammadex formulations complexes with steroidal neuromuscular blockers drugs Rocuronium and Vecuronium

Abstract

Sugammadex a modified γ-cyclodextrin forms strong water-soluble complexes with steroid neuromuscular blockers (NMBs) such as Rocuronium and Vecuronium, creating a concentration gradient that favors the displacement of these drugs from the neuromuscular junction to the plasma, quickly reversing the neuromuscular obstruction. This work described the comparative evaluation between two formulations of Sugammadex solution from Blau Farmacêutica S/A compared to reference formulation Bridion^®, by Nuclear Magnetic Resonance (NMR) ¹H and DOSY techniques. The formulations were evaluated in presence of Rocuronium and Vecuronium in the stoichiometric proportions of 1:1 and 1:0.4 for both NMBs. NMR ¹H spectra of the formulations Blau and Bridion^® did not show significant variations of chemical shifts showing similar physicochemical parameters. Chemical shifts and diffusion coefficients of NMBs were influenced by the presence of Sugammadex when compared to NMBs formulations in the absence of any cyclodextrin, directly demonstrating the strong intermolecular interaction associated with the host molecule in a high proportion. No significant variation in the diffusion coefficients of the key components between formulations in the presence of NMBs in the equimolar 1:1 and 1:04 w/w ratios was observed. The constants K_a and K_D were determined and presented 16.7 and 0.06 mM values respectively, according to literature for this system.