Crystal structure of Norfloxacin and characterization of its polymorphism forms

LUCAS CHIERENTIN; TAHISA PEDROSO; CLAUDIA GARNERO; MARCELA LONGHI; HERIDA SALGADO

Congreso; II Congreso Farmacéutico da UNESP; 2012

Faculdade de Ciencias Farmacéuticas

Introduction: Norfloxacin (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazinyl)-3-quinoline carboxylic acid) is a synthetic antibacterial fluoroquinolone related to nalidixic acid. It is one of the most active fluoroquinolones with a wide spectrum of activity used in the treatment of gonorrhea and prostate and urinary tract infections. The study of polymorphism is an important factor for the pharmaceutical industry. Objective: The aim of this study was to obtain crystals of norfloxacin and to characterize their shapes. Methodology: Various polymorphic forms of norfloxacin were obtained using three different solvents. Were weighed 1 g of norfloxacin and solubilized in 100.0 mL of acetonitrile, isopropanol and acetone, separately at reflux for three hours. Once the solid was dissolved, it was allowed to slowly cool to room temperature at a rate of 4 °C each day. All crystals have been characterized by X-ray crystallography (the samples were analyzed in X-ray diffractometer model Siemens D500, with a scan rate 0.1°/seconds each 0.05° in 2 theta, ranging from 4° to 70°, used rafiation of Cu by crystal monocromatizada graphite), thermal nalysis (Differential scanning calorimetry- DSC; Thermogravimetry- TG, the samples were placed in aluminum capsules partially closed with a heating of 10°C/min in range 25-350°C, a dynamic atmosphere of nitrogen at a flow rate of 70 mL/min, Al3O3 support; prior the analyzes there was instrument calibration using a sample of calcium oxalate monohydrate with mass losses defined), absorption spectroscopy in the infrared region (IR), nuclear magnetic resonance (NMR) and scanning electron microscopy- SEM (the samples were plating with gold to make the conductive surface and placed in a sample port for evaluation, using an electron microscope brand JEOL model JSM-7500F). Results and discussion: All of these techniques confirmed the obtaining of three polymorphism forms: A, B and C. Many drugs exhibit polymorphism and their physical forms are vital for obtaining the desired therapeutically effective product. The guide of International Conference on Harmonization (ICH) Q6A is related to polymorphism and defines the specifications of new drugs and medicines, this definition included the salvation or hydration of drugs (pseudo-polymorphism) and amorphous forms. In conclusion, then, that forms A and B are anhydrous forms and C an amorphous form of norfloxacin. This can be important because many commercial samples of norfloxacin are provided as the metastable form at room temperature, and then, undesirable transformations could occur and modify its therapeutic activity.