Solubilization of sulfamerazine by complexation with cyclodextrins

ALOISIO, CAROLINA; DELRIVO, ALICIA; ZOPPI, ARIANA; LONGHI, MARCELA RAQUEL

Ribeirao Preto, SP, Brazil

Congreso; 7th Internacional Congress of Pharmaceutical Sciences; 2009

INTRODUCTION. Sulfamerazine (SMR) is an antibacterial, which like many sulphonamides, is sparingly soluble in water. The poor aqueous solubility of the drug gives rise to difficulties in the pharmaceutical formulation. To overcome this drawback, the increase of the aqueous solubility of SMR was very important. Cyclodextrins (CDs) are cyclic oligosaccharides used in pharmaceutical formulations to enhance solubility, dissolution rate, stability and bioavailability by means of the formation of inclusion complexes. The OBJECTIVE of the present work was to study the complexation of SMR utilizing two different cyclodextrins (Me-B-CD and B-CD) to improve the solubility and to determine the effect of the complexation in solid state. METHODS. The binding constants (KS) and the stoichiometry for the complexes were determined in water and in buffer solutions of pH 2 and 8, by means of phase-solubility studies. The different pH values were used to study the influence of the ionization state of the drug on the complexation with CDs.  In solid state, the binary systems, prepared by means of simple physical mixture or by lyophilization, were studied by Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC) and Termogravimetry (TG). RESULTS.  With both CDs were obtained soluble complexes of type AL, indicating the presence of 1:1 host–guest complexes, except with B-CD at pH 8. In this last case, curves of type AN were obtained denoting the formation of 2:1 host-guest complexes (according to Higuchi and Connors). Me-B-CD demonstrated to confer a high solubility to the drug, regarding the B-CD. In turn, a higher solubility is achieved using a combined approach of pH adjustment and complexation with CDs, since the ionic drug has higher water solubility compared with that of the noionised one. The results obtained with IR, DSC and TG show that true inclusion complexes, SMR:B-CD and SMR:Me-B-CD are formed, when they were prepared by means of lyophilization.  CONCLUSIONS. An important increment in water solubility was obtained for SMR, mainly in the case of the complexes formed with Me-B-CD, which will allow the use of these complexes in the formulation of pharmaceutical products containing this drug as active ingredient.