Study of the effect of B-cyclodextrin on the stability of norfloxacin C

CLAUDIA GARNERO; ANA K. CHATTAH; LUIS FABIETTI; MARCELA R. LONGHI

Córdoba

Conferencia; 3° Reunión Internacional de Ciencias Farmacéuticas; 2014

Universidad Nacional de Córdoba

The polymorphism, the ability of a molecule to exist in several different conformations, affects the chemical and physical properties of an active pharmaceutical ingredient (API), which have a significant impact on pharmaceutical profile. A strategy developed to improve solubility, stability, and bioavailability of APIs is the formation of complexes with cyclodextrins (CDS). Norfloxacin (NOR) is a synthetic broad antibacterial fluoroquinolone that exists in several solid forms. In this study NOR form C was select as API model. Preliminary reports showed that supramolecular systems with B-cyclodextrin (B-CD) as ligand were developed to optimize physicochemical properties of APIs. In the present work, the effect of novel supramolecular systems on chemical and physical stability of NOR C in solid state was investigated. The stability of NOR form C, the NOR C:B-CD system obtained by kneading method and their physical mixture was evaluated under accelerated storage conditions (at 40 C and 75% relative humidity). Then, the solid samples were stored in closed glass vials exposed to daylight over a 6 month period into a chamber stability. The samples at predetermined intervals were monitored. In particular, the chemical stability was monitored by high performance liquid chromatography (HPLC), while solid state nuclear magnetic resonance (ssNMR) and powder X-ray diffraction (PXRD) were used to evaluate the physical stability and possible phase transformations. In addition, the hygroscopicity was determined. Our results revealed that NOR C and the physical mixture suffered the chemical degradation process. While, the amount of NOR C remains constant in the NOR C:B-CD system, indicating that the interaction between B-CD and NOR C increase the stability of the polymorph. In conclusion, the NOR C:B-CD system constitute an tool alternative to improve physicochemical properties of this polymorph, with potential application for the preparation of pharmaceutical dosage products.