DEVELOPMENT OF CHLORAMPHENICOL SUPRAMOLECULAR SYSTEMS TO IMPROVE DISSOLUTION RATES

CIOCHETTO GEORGINA; STERREN VANESA; LONGHI MARCELA; ZOPPI ARIANA

Córdoba

Congreso; 3a Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2014

Chloramphenicol (CP), a lipophilic antibiotic, has poor solubility and dissolution rate in aqueous solution, which affects its application in clinical therapy. In this contribution, CP supramolecular systems with aminoacids (AA) were prepared by different methods: freeze-dried (M I) and drop assisted grinding (M II). In solid state, the systems were characterized by X-ray diffraction (XRD), Fourier transform infrared (IR) spectroscopy and confocal laser scanning microscope (CLSM). In addition, the dissolution rate studies of CP (alone and from CP/AA systems) were conducted in a dissolution apparatus using the paddle method, in 900 ml simulated gastric fluid without enzime, at 37 ± 0.5 ºC and stirring at 50 r/min. When CP is processed with leucine or arginine maintains its crystalline structure, but shows different crystal habit. The CLSM images showed that crystal shape was changed and particle size was reduced, compared to control untreated drug. The crystals obtained from M I produced rods shaped crystals and that obtained from M II exhibited irregular surfaces with a tendency to form agglomerates. The IR spectra of CP/AA systems showed the same characteristic vibrations for CP observed in the raw materials and no molecular interactions between the drug and AA could be detected. The dissolution rate of newly developed solid forms was found to be greater than the pure drug. It was concluded that the supramolecular systems with both AA showed improved dissolution rate compared to the pure CP. These increases in dissolution appear to be derived from a combination of changes to crystal habit and particle size.