Characterization and in vivo efficacy of inclusion complexes of sulphadoxine with β-cyclodextrin: calorimetric and spectroscopic studies

The study reports the characterization and pharmacological activity of sulphadoxine which is encaged by β-CD and its hydroxypropyl and methyl derivatives. Phase solubility studies depict AL type of curves suggesting 1:1 complexation. Inclusion of drug in solid state was evidenced by Differential scanning calorimeter (DSC), Powder X-ray diffractometery (PXRD), Fourier transform infrared spectroscopy (FTIR) and in solution phase by NMR and solution calorimetry. In the proton NMR chemical shifts of aniline ring and methoxy group of pyrmidine ring moved downfield upon inclusion indicating the potentiality of both sides of the drug to interact with the cavity. Insertion of whole of the drug molecule inside the cavity is ruled out because of its three dimensional (3D) structure. Thus, co-existence of two 1:1 complexes is proposed in the present study. The calorimetric data are fitted into two class binding model to evaluate the values of stability constants (K 1 and K 2) along with enthalpy of binding (∆H 1 and ∆H 2). Efficiency of the encaged drug was evaluated by in vitro drug release studies and provided useful information for the selection of appropriate form for further studies. The best performance in terms of dissolution rate enhancement was displayed by the Sulpha-M-β-CD lyophilized product. This was further evaluated on the basis of its pharmacological activity using Balb/C mice and showed significantly higher survival rate (83.3%) after 30 days as to the uncomplexed drug which showed (33%) survival.