Evaluation of the antimicrobial activity of Norfloxacin polymorphisms through the turbidimetric method

LUCAS CHIERENTIN; ELIANE TOTOLI; CLAUDIA GARNERO; MARCELA LONGHI; HERIDA SALGADO

Congreso; II Congreso Farmacéutico da UNESP; 2012

Faculdade de Ciencias Farmacéuticas

Introduction: Fluoroquinolones are an important class of antibacterials, which have been developed rapidly in recent years and have wide applications in clinical medicine. Norfloxacin is a synthetic fluoroquinolone derivative of nalidixic acid, which has demonstrated broad-spectrum activity against many pathogenic Gram-negative and Gram positive bacteria. The study of drug polymorphism has become vital, as it can directly affect the drugs in vivo performance. Considering this impact, new methods have been evaluated to predict the nature of drug polymorphism, both during drug and product development stages. Objetive: The objective of this study was to analyze the antimicrobial activity of three polymorphic forms of the antimicrobial norfloxacin by turbidimetric method. Methodology: Casoy agar was used for maintenance of microorganism Staphylococcus epidermidis ATCC 12228 IAL 2150 and BHI broth for microbiological testing. The inoculums was prepared 24 hours prior to the experiment. The polymorphic forms A, B and C of norfloxacin were tested against the NOR-MP. Similar tubes containing 10.0 mL of sterile BHI broth, 200.0 mL of each solution at concentrations of 25, 50 and 100.0 mL and 600.0 mL of inoculums were added. These tubes were incubated in a shaker with waterbath at a temperature of 35.0 °C for 4 hours. After the incubation period, the multiplication of microorganisms was interrupted by the addition of 500 mL of 12% formaldehyde solution in each tube. Absorbance was determined for each tube in a spectrophotometer. Results and discussion: The analysis of samples of polymorphic forms A, B and C were compared to samples of NOR-MP, by the turbidimetric method developed and validated. The potency was calculated by equation Hewitt (Antilog M x 100). The results showed that free norfloxacin had a potency of 102.5% and samples with A, B and C had potencies of 91.5, 107.66 and 57.87%, respectively. In conclusion, the form B showed a better activity than NOR-MP, although the form C showed less activity. This means that changes in the physical form of the drug may alter the microbiological activity. Polymorphism fo an active pharmaceutical ingredient may have an influence on various properties, such as solubility, bioavailability and stability. Therefore, investigations of polymorphism and pseudopolymorphism, comparisons of physicochemical properties of such forms and clarifying transformation between crystalline forms, are important parts of preformulation study.