DEVELOPMENT OF CHLORAMPHENICOL SUPRAMOLECULAR SYSTEMS TO IMPROVE DISSOLUTION RATE

CIOCHETTO, G.; STERREN, V.B.; LONGHI, M. R.; ZOPPI, A.

Córdona

Congreso; 3° Reunión Internacional de Ciencias Farmacéuticas; 2014

Chloramphenicol (CP), a lipophilic antibiotic, exhibits a poor solubility and dissolution rate in aqueous solution, feature that limits its clinical application. In this context, the aim of this study was to enhance the dissolution rate of CP by the preparation of supramolecular systems with different aminoacids (AA). In this work, CP supramolecular systems containing leucine or arginine were prepared by different methods, such as drop assisted grinding and freeze-drying, with the resulting solid materials being characterized by X-ray diffraction, Fourier transform infrared spectroscopy (IR) and confocal laser scanning microscopy (CLSM). In addition, dissolution rate studies of both CP and CP/AA systems were conducted using a dissolution apparatus applying the paddle method. Tests were performed in 900 ml of simulated gastric fluid without enzymes, at 37.0±0.5 ºC and stirring at 50 rpm. When CP was formulated with leucine or arginine, it maintained its crystalline structure but a different crystal habit was found. CLSM images evidenced that the crystal shape of CP changed upon combination with AA, bearing also a reduction of its particle size. The crystals obtained by the drop assisted grinding method exhibited irregular surfaces with a tendency to form agglomerates, while the freeze-drying method produced rod shaped crystals. IR spectra obtained for the CP/AA systems showed the same characteristic vibrations as those observed for pure CP, with no intermolecular interactions being detected between the drug and AA. Finally, the dissolution rate of the binary systems was higher than that of the pure drug. It was concluded that the supramolecular systems of CP with leucine and arginine exhibited improved dissolution rate compared to the pure compound, feature that appear to derived from a combination of changes in the crystal habit and a reduction of the particle size.