Asunto(s)
Proteínas Bacterianas/genética , Análisis Mutacional de ADN , ARN Polimerasas Dirigidas por ADN/genética , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/genética , Pruebas en el Punto de Atención , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Antibióticos Antituberculosos/uso terapéutico , Genotipo , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/patogenicidad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
The aim of the investigation is to improve the dissolution, wettability, and micromeritic behavior of domperidone, a dopamine antagonist, used in the treatment of nausea and vomiting. Micropelletization technique, a possible approach for ensuring maximum dissolution with enhanced wettability, and uniform pellet size almost spherical so as to achieve the smooth gastric transit of drug have been estimated. Micropellets were prepared utilizing solvent diffusion technique and all the process parameters such as solvent-non-solvent ratio, stirring speed, temperature, and effect of aggregating agent on the micropellets formulation have been optimized. The addition of an aggregating agent (10%v/v of isopropyl alcohol) improved the uniform micropellets formation and the method was reproducible. The micromeritic properties such as size distribution, surface property (using Scalar-USB digital photomicroscope), packability, and flowability of the formulated micropellets were characterized. Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetric (DSC) analysis were performed to explain the results. Formulated micropellets showed clear and highly improved in vivo dissolution behavior, probably due to high wettability. The micropelletized drug was stable at room temperature, 25 degrees C/60% relative humidity (RH), and 45 degrees C/70% RH, after 12 weeks.
Asunto(s)
Química Farmacéutica/métodos , Domperidona/química , Rastreo Diferencial de Calorimetría , Tamaño de la Partícula , Polvos , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , HumectabilidadRESUMEN
We have investigated the effect of nitrogen laser irradiation (337 nm) on viability of clinical isolates of Mycobacterium tuberculosis. Bacteria were exposed to a nitrogen laser (average power 2.0 mW) in vitro at power density of 70 +/- 0.7 W/m2 for 0-30 min, and the cell viability was determined by luciferase reporter phage (LRP) assay. Immediately after laser exposure, all the clinical isolates investigated showed a dose-dependent decrease in cell viability. However, when the laser-exposed isolates were incubated in broth medium for 3 days, most of these showed significant recovery from laser-induced damage. Addition of 5.0 microg/ml acriflavine (a DNA repair inhibitor) in the incubation medium had no significant effect on recovery. This suggests that DNA damage may not be involved in the cell inactivation. Electron paramagnetic resonance (EPR) studies using 5-doxyl strearic acid (5-DS) as a probe suggest alterations in lipid regions of the cell wall. Implications of these results for understanding therapeutic effect of nitrogen laser on drug-resistant tuberculosis are discussed.
