Inclusion complexes of cefuroxime axetil with β-cyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on complexation

Abstract

The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil (CFA), were prepared with β-cyclodextrin (βCD) with or without addition of l-arginine (ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency (CE) of βCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL (linear) type of solubility curve in presence and absence of ARG, the CE and association constant (Ks) of βCD towards CFA were significantly promoted in presence of ARG, justifying its use as a ternary component. The solid systems of CFA with βCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), and saturation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA inside βCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation with βCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclusion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA via βCD complexation.

Computer-Aided Design of Cefuroxime Axetil/Cyclodextrin System with Enhanced Solubility and Antimicrobial Activity

“…In the FT-IR spectra, the most visible changes were observed in the intensities of bands from the CA carbonyl groups, which tends to interact with HPβCD hydroxyl groups [32]. The results of this study correlate with those obtained by Sapte, who also complexed CA with βCD using the spray-drying technique with or without the addition of L-arginine [8].…”

“…The in silico studies allowed to rank CA-CD systems by predicted affinities, thus to select the most favorable system. According to the published thermodynamic effect of complexation in the studies of CA-HPβCD (Ks = 382.7 M −1 ) [7] and CA-βCD (Ks = 339.7 M −1 ) [8], the predicted ranks 1 and 3, respectively, remain in agreement with experimental results. In the literature, good agreement of in silico predictions with experimental results was observed for Ibuprofen systems with β−, γ−, and HPβCD, where dG of binding was simulated with the MM-PBSA approach [30].…”

“…In the study of Shah et al, CA was complexed with hydroxypropyl-βCD (HPβCD), resulting in improved solubility [7]. A recent study on the CA-βCD system also showed an increase in the solubility of CA in the system relative to pure CA [8]. The findings related to the high stability of CA-HPβCD are consistent with the increased bioavailability of the system compared to pure CA, reported by Prabhakaran et al [9].…”

in silico and Physico-Chemical Assessment of Effectiveness of Hydroxy/Amino Acids as Auxiliary Substances to Improve the Complexation Efficiency of ββ ββ β-Cyclodextrin Towards Bosentan

“…The crystalline nature of bosentan monohydrate and βCD was clearly visible from their respectrive thermograms with sharp melting endotherm at 115 and 120 °C, respectively. DSC thermogram of L-arginine indicated broad endothermic peaks at 49.36 °C, 99.97 °C and sharp endothermic peak at 222.64 °C due to dehydration of L-arginine and crystalline nature of it respectively [14,21]. In case of binary and ternary complexes, disappearance of bosentan monohydrate melting peaks were observed indicating the entrapment of bosentan monohydrate inside the β-cyclodextrin cavity confirming formation of inclusion complexes [25].…”

“…The possible stoichiometries for all systems were found to be 1:1. The phase solubility parameters are displayed in Table-1 effectiveness as a ternary substance than others in terms of K s and complexation efficiency [15,21]. in silico Studies: in silico Studies were performed for the prediction of most stabilized structure and to check out the involvement of certain non-bonded forces of interactions during complexation process.…”