RESUMO
This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.
Assuntos
Antibacterianos , Ciprofloxacina , Polieletrólitos , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/urina , Ciprofloxacina/administração & dosagem , Ciprofloxacina/química , Ciprofloxacina/farmacocinética , Ciprofloxacina/urina , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Método Duplo-Cego , Liberação Controlada de Fármacos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Polieletrólitos/administração & dosagem , Polieletrólitos/química , Polieletrólitos/farmacocinética , Comprimidos , Adulto JovemRESUMO
Carbomer hydrogels 971pNf, 934pNf and 940Nf loaded with ofloxacin were characterized and their antimicrobial properties evaluated. bactericidal profiles show improved efficacy and prolonged activity exhibited by ofloxacin-containing hydrogels against Pseudomonas aeruginosa. Analysis of bactericidal index (BI) values after a short time of drug exposure confirms the higher potency of hydrogels compared with that of ofloxacin. Increased BI values observed after 24 h indicate prolonged action against the microorganisms evaluated. The bacterial uptake of ofloxacin from hydrogels was higher than that obtained with a solution of free ofloxacin in both fluoroquinolone-sensitive and -resistant P. aeruginosa. The improved uptake in fluoroquinolone-resistant isolates was correlated with the viscosity of hydrogels. The performance of hydrogels seems to be related to their bioadhesive properties that allow prolonged contact time and the release of an effective amount of drug close to bacterial cells. Hence, hydrogels could be used in the development of more effective formulations for topical administration of antibiotics. Improved performance of an old antibiotic can preserve the use of new generation fluoroquinolones.
Assuntos
Antibacterianos/metabolismo , Antibacterianos/farmacologia , Ofloxacino/metabolismo , Ofloxacino/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Resinas Acrílicas , Adesividade , Ciprofloxacina/metabolismo , Ciprofloxacina/farmacologia , Fluoroquinolonas/metabolismo , Fluoroquinolonas/farmacologia , Humanos , Hidrogéis , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/metabolismo , Reologia , ViscosidadeRESUMO
The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure-activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Fluoroquinolonas/química , Fluoroquinolonas/farmacologia , Relação Quantitativa Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Fluoroquinolonas/síntese química , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Sulfonamidas/síntese química , BenzenossulfonamidasRESUMO
Two new quinolones, NSFQ-104 and NSFQ-105, derivatives of ciprofloxacin and norfloxacin with a 4-(4-aminophenylsulphonyl)-1-piperazinyl at position 7 showed better in-vitro activity against strains of methicillin-susceptible and methicillin-resistant Staphylococcus aureus than ciprofloxacin or norfloxacin. Their in-vitro activity was enhanced at pH 5.5.