Preparation and characterization of sulfamethazine multicomponent complexes

ZOPPI A.; LONGHI, M. R.

Brasilia

Congreso; V Congreso Iberoamericano de Ciencias Farmacéuticas, XV Conferencia Iberoamericana de Facultades de Farmacia (COIFFA); 2013

Introduction: Sulfamethazine (SMT) is a drug used in the treatment of infections arising from Gram-positive and Gram-negative organisms. However, the water solubility of SMT is low and consequently reduces its bioavailability.1 The complexation with Bcyclodextrin (BCD) in presence of auxiliary substances is a commonly applied approached to increase the solubility of a poorly soluble compounds.2 Based on the above-mentioned considerations, the aim of the present series of experiments was to investigate the combined effect of BCD and different amino acids [arginine (Arg), aspartic acid (Asp), glutamic acid (Glu), isoleucine (Ile), leucine (Leu) and valine (Val)] on the enhancement of SMT aqueous solubility. Materials and Methods: The effects of complexation on drug solubility, affinity constant (KC) and the stoichiometry for the complexes were determined in water, by means of phase-solubility studies. In solid state, the ternary systems, prepared by means of simple physical mixture (PM) or by freeze-drying (FD), were studied by fourier-transform infrared spectroscopy (FT-IR), and thermal analysis [differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)]. Results and Discussion: For all systems studied, a linear increase in SMT solubility occurred at different BCD concentrations, exhibiting an AL-type profile with 1:1 stoichiometry. The efficiency of solubility (ES, Smax/S0) and KC values calculated from each phase-solubility diagrams are presented in Table 1. The difference in the KC values observed upon addition of each amino acid shows that they are able to interact in a different way with SMT:BCD complexes depending on their structures. The complexation with BCD in presence of Leu proved to have better solubilizing and complexing properties for SMT than the others amino acids, as could be stated by the higher KC value obtained for this system. Based on the results obtained in the phase-solubility experiments, the ternary complex with Leu was used to carry out the studies in solid state. The results obtained by FT-IR, DSC and TG confirmed the formation of a complex between SMT and BCD in presence of Leu, when the system was prepared by applying a FD method. Conclusion: The results obtained in this work showed that the interaction of SMT with BCD and amino acids, leads to important modifications on the solubility of the guest molecule, which might eventually have relevant pharmaceutical potential. References: 1) Sweetman, SC, Blake, PS. (2009). Martindale: The Complete Drug Reference. Pharmaceutical Press. 2) Loftsson, T, Brewster, ME. (2012). J. Pharm. Sci., 101(9), 3019-3032.