RESUMEN
The literature reveals gaps in the availability of green analytical methods for assessing products containing gatifloxacin (GFX), a fluoroquinolone. Presently, method development is supported by tools such as the National Environmental Methods Index (NEMI) and Eco-Scale Assessment (ESA), which offer objective insights into the environmental friendliness of analytical procedures. The objective of this work was to develop and validate a green method by the NEMI and ESA to quantify GFX in eye drops using HPLC. The method utilized a C8 column (4.6 × 150 mm, 5 µm), with a mobile phase of purified water containing 2% acetic acid and ethanol (70:30, v/v). The injection volume was 10 µL and the flow rate was 0.7 mL/min in isocratic mode at 25°C, with detection performed at 292 nm. The method demonstrated linearity in the range of 2-20 µg/mL, and precision at intra-day (relative standard deviation [RSD] 1.44%), inter-day (RSD 3.45%), and inter-analyst (RSD 2.04%) levels. It was selective regarding the adjuvants of the final product (eye drops) and under forced degradation conditions. The method was accurate (recovery 101.07%) and robust. The retention time for GFX was approximately 3.5 min. The greenness of the method, as evaluated by the NEMI, showed four green quadrants, and by ESA, it achieved a score of 88.
Asunto(s)
Gatifloxacina , Tecnología Química Verde , Límite de Detección , Soluciones Oftálmicas , Gatifloxacina/análisis , Gatifloxacina/química , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Tecnología Química Verde/métodos , Modelos Lineales , Soluciones Oftálmicas/química , Soluciones Oftálmicas/análisis , Fluoroquinolonas/análisis , Fluoroquinolonas/químicaRESUMEN
Novel restricted access molecularly imprinted nanomaterials (RAMIPs) were successfully prepared on the surface of metal-organic frameworks (NH2-MIL-125) by surface-initiated atom transfer radical polymerization (SI-ATRP) technology. Then it was applied as a solid phase extraction (SPE) material in analysis of quinolones in bovine serum by HPLC detection. NH2-MIL-125@RAMIPs was empolyed as a sorbent for gatifloxacin (GTFX) and the resulted material has a good binding amounts (86.1 mg g-1), rapid binding kinetic (36 min). The results indicated that the prepared NH2-MIL-125@RAMIPs possess excellent specific recognition for GTFX. Combined with high-performance liquid chromatography (HPLC), the SPE column filled with NH2-MIL-125@RAMIPs was applied to selectively enrich GTFX antibiotic from bovine serum. The recovery of GTFX is between 96.8% and 105.6%, with relative standard deviations of 1.7-3.2% (n = 3). The research results illustrate that the method is successfully applied to the selective enrichment of GTFX in bovine serum. It provides a simple and efficient method for the direct detection of GTFX in bovine serum.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Gatifloxacina , Estructuras Metalorgánicas/química , Impresión Molecular/métodos , Extracción en Fase Sólida/métodos , Animales , Bovinos , Gatifloxacina/sangre , Gatifloxacina/química , Gatifloxacina/aislamiento & purificación , Límite de Detección , Modelos Lineales , Reproducibilidad de los ResultadosRESUMEN
Loading of gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and gatifloxacin loading capacity as well as sustained drug delivery. Optimization of gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and gatifloxacin loading capacity of 92.56 µg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo gatifloxacin release data for rabbit tear fluid showed sustained release with a high gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.
Asunto(s)
Lentes de Contacto Hidrofílicos , Sistemas de Liberación de Medicamentos/métodos , Gatifloxacina/farmacocinética , Absorción Ocular/efectos de los fármacos , Soluciones Oftálmicas/farmacocinética , Poloxámero/farmacocinética , Animales , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos/efectos de los fármacos , Liberación de Fármacos/fisiología , Excipientes/administración & dosificación , Excipientes/química , Excipientes/farmacocinética , Femenino , Gatifloxacina/administración & dosificación , Gatifloxacina/química , Masculino , Absorción Ocular/fisiología , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/química , Poloxámero/administración & dosificación , Poloxámero/química , ConejosRESUMEN
The supercritical impregnation process was used as a green technology for the elaboration of drug delivery intraocular lenses to mitigate the risk of post-operatory endophthalmitis after cataract surgery. Commercially available hydrophobic acrylic (copolymer of benzyl methacrylate and methyl methacrylate) intraocular lenses (IOLs) were impregnated with gatifloxacin, a fourth generation fluoroquinolone drug, using pure supercritical CO2 (scCO2) to obtain solvent-free loaded implants. The interaction phenomena involved in the supercritical impregnation were studied by following in situ scCO2 sorption within the polymer support and the subsequent IOL swelling, and by taking into account drug solubility in the supercritical fluid phase. The drug impregnation yields determined though in-vitro release studies varied between 0.33 and 1.07 ± 0.07 µg·mg-1IOL in the studied experimental conditions (8 to 25 MPa, 308 to 328 K and 30 to 240 min impregnation duration). An impregnation duration longer or equal to the time required for a complete CO2 uptake by the polymer as well as a higher pressure or a higher temperature over the crossover pressure delimiting the upper limit of the retrograde solubility zone, led to higher drug impregnation yields.
Asunto(s)
Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Endoftalmitis/prevención & control , Gatifloxacina/administración & dosificación , Lentes Intraoculares/efectos adversos , Dióxido de Carbono/química , Endoftalmitis/etiología , Gatifloxacina/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Polímeros/química , Solubilidad , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and represents one of the leading causes of mortality worldwide due to multidrug-resistant TB (MDR-TB). In our work, a new formulation of biodegradable PLGA microparticles was developed for pulmonary administration of gatifloxacin, using a surface modifier agent to actively target alveolar macrophages thereby allowing to gain access of the drug to Mycobacterium tuberculosis. For this, rapid uptake of the particles by macrophages is beneficial. This process was evaluated with fluorescein-loaded microparticles using PLGA 502 or PLGA 502H as polymers and labrafil as surface modifier. Cell phagocytosis was studied in raw 264.7 mouse macrophage cell line after 3, 5, 24, and 48 h incubation with the microparticles. Labrafil enhanced the uptake rate of PLGA 502H microparticles by macrophages which was directly related to the modification of the polymer matrix. Gatifloxacin-loaded PLGA microparticles using PLGA 502 or PLGA 502H and labrafil were prepared. From our results, only microparticles prepared with PLGA 502H and labrafil exhibited high encapsulation efficiency (89.6 ± 0.2%), rapid phagocytosis by macrophages (3 h), and remained inside the cells for at least 48 h, thereby resulting in a suitable carrier to potentially treat MDR-TB.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Gatifloxacina/administración & dosificación , Macrófagos/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/administración & dosificación , Animales , Gatifloxacina/química , Macrófagos/fisiología , Masculino , Ratones , Microscopía Electrónica de Rastreo/métodos , Microesferas , Mycobacterium tuberculosis/fisiología , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Células RAW 264.7 , Propiedades de Superficie , Tuberculosis/tratamiento farmacológicoRESUMEN
A series of gatifloxacin-1,2,3-triazole-isatin hybrids 8a-l were designed, synthesized, and screened for their in vitro antimycobacterial activity as well as cytotoxicity toward Chinese Hamster Ovary (CHO) cells. The synthesized hybrids showed considerable activity against MTB H37 Rv and two MDR-MTB strains with minimal inhibitory concentration (MIC) of 0.25-8 µg/ml, and the hybrid 8a (MICMTB H37Rv : 0.25 µg/ml and MICMDR-MTB : 0.5 and 1 µg/ml) was found to be most active against the tested strains, which was not inferior to the parent gatifloxacin (MIC: 0.5, 0.25, and 0.5 µg/ml) against all three tested strains, and was ≥128-fold more active than isoniazid (MIC: ≥64 µg/ml) and rifampicin (MIC: >128 µg/ml) against the two MDR-MTB strains. Moreover, hybrid 8a (CC50 : 8.0 µg/ml) also displayed acceptable cytotoxicity toward CHO cells, and the selectivity index was 32. The structure-activity relationship and structure-cytotoxicity relationship were also enriched.
Asunto(s)
Antituberculosos/síntesis química , Diseño de Fármacos , Gatifloxacina/química , Isatina/química , Mycobacterium tuberculosis/efectos de los fármacos , Triazoles/síntesis química , Animales , Antituberculosos/química , Antituberculosos/farmacología , Antituberculosos/toxicidad , Células CHO , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Triazoles/química , Triazoles/farmacología , Triazoles/toxicidadRESUMEN
The optical and swelling properties of gatifloxacin-loaded contact lens decrease owing to the precipitation of gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the gatifloxacin precipitates and not limited to sustain the release of gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X1, %w/v), the concentration of Pluronic F68 in the packaging solution (X2, %w/v), the concentration of gatifloxacin incorporated in the monomer solution (X3, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during autoclave (X4, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during extraction (X5, %w/v), the time (stabilization time) after the addition of gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X6, h), the pH of the packaging solution (X7), the temperature of the extracted solution (X8, °C), and the curing time for fabricating the contact lens (X9, min). The gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y1, %), optical transmittances after 7â¯days of sterilization (Y2, %) and swelling percentages after 7â¯days of sterilization (Y3, %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y1, Y2, and Y3, respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X1) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X2) improved them through micelle formation. The other variables (X3 to X9) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of gatifloxacin-loaded contact lens.
Asunto(s)
Lentes de Contacto , Gatifloxacina/química , Poloxámero/química , Preparaciones de Acción Retardada/química , Diseño de Fármacos , Embalaje de Medicamentos , Micelas , EsterilizaciónRESUMEN
Self-assembled particles, based on non-covalent interactions, are attractive drug carriers with a relatively simple structure and easy preparation. Tannic acid (TA) is an anionic polyphenolic compound with a wide range of molecular interactions and diverse applications in drug delivery research. Here, we propose the use of TA complexes with cationic antibiotics as a new pH-responsive drug carrier of high drug loading and optimal stability. TA complexes were prepared with three water-soluble antibiotics; colistin sulfate (COL), gentamicin sulfate (GEN) and gatifloxacin (GAT). Complexes' size ranged from several-hundred nanometers to few microns. For selected particles, drug loading ranged from 30 to 36%. Importantly, we demonstrate the impact of drug-carrier interactions, studied via infrared spectroscopy and molecular modeling, on final complex stability and performance; the complexes resisted dissociation in presence of serum at physiological pH to variable degrees and showed different drug release profiles. However, all complexes dissociated upon medium acidification, releasing their drug payload and demonstrating expected antibacterial effect. These results demonstrate that TA/antibiotic self-assembled complexes represent an excellent carrier for pH-sensitive delivery of water-soluble drugs. In addition to system's simplicity and low cost, complexes were easily prepared with high drug loading and desirable pH-dependent association/dissociation profile.
Asunto(s)
Antibacterianos , Portadores de Fármacos , Taninos , Antibacterianos/administración & dosificación , Antibacterianos/química , Colistina/administración & dosificación , Colistina/química , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Liberación de Fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Gatifloxacina/administración & dosificación , Gatifloxacina/química , Gentamicinas/administración & dosificación , Gentamicinas/química , Concentración de Iones de Hidrógeno , Modelos Moleculares , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Taninos/administración & dosificación , Taninos/químicaRESUMEN
A highly accurate and precise spectrofluorimetric method was established for quantitation of Gatifloxacin in pure material, pharmaceutical formulations and in the existence of its oxidative degradation product. The emission was recorded at 487â¯nm after the excitation at 290â¯nm. Using micelle, sodium dodecyl sulphate (SDS), enhanced fluorescence intensity of Gatifloxacin-SDS complex. The optimization of numerous experimental conditions was carried out. The improved emission showed a suitable linear correlation between derivative synchronous fluorescence power and concentration of Gatifloxacin over the range of 10 to 100â¯ng/mL with a determination coefficient equals 0.9996. Studying cytotoxicity and antimicrobial susceptibility for oxidative degradation product of Gatifloxacin was carried out using Gatifloxacin as a control. In comparison, the proposed method presented a superior sensitivity and enhanced stability over the reported method.
Asunto(s)
Gatifloxacina/análisis , Espectrometría de Fluorescencia/métodos , Bacterias/efectos de los fármacos , Estabilidad de Medicamentos , Gatifloxacina/química , Gatifloxacina/farmacología , Límite de Detección , Modelos Lineales , Pruebas de Sensibilidad Microbiana , Oxidación-Reducción , ComprimidosRESUMEN
To overcome the increased disease rate, utilization of the versatile broad spectrum antibiotic drugs in controlled drug-delivery systems has been a challenging and complex consignment. However, with the development of microemulsion (µE)-based formulations, drugs can be effectively encapsulated and transferred to the target source. Herein, two biocompatible oil-in-water (o/w) µE formulations comprising clove oil/Tween 20/ethylene glycol/water (formulation A) and clove oil/Tween 20/1-butanol/water (formulation B) were developed for encapsulating the gatifloxacin (GTF), a fourth-generation antibiotic. The pseudoternary phase diagrams were mapped at a constant surfactant/co-surfactant (1:1) ratio to bound the existence of a monophasic isotropic region for as-formulated µEs. Multiple complementary characterization techniques, namely, conductivity (σ), viscosity (η), and optical microscopy analyses, were used to study the gradual changes that occurred in the microstructure of the as-formulated µEs, indicating the presence of a percolation transformation to a bicontinuous permeate flow. GTF showed good solubility, 3.2 wt % at pH 6.2 and 4.0 wt % at pH 6.8, in optimum µE of formulation A and formulation B, respectively. Each loaded µE formulation showed long-term stability over 8 months of storage. Moreover, no observable aggregation of GTF was found, as revealed by scanning transmission electron microscopy and peak-to-peak correlation of IR analysis, indicating the stability of GTF inside the formulation. The average particle size of each µE, measured by dynamic light scattering, increased upon loading GTF, intending the accretion of drug in the interfacial layers of microdomains. Likewise, fluorescence probing sense an interfacial hydrophobic environment to GTF molecules in any of the examined formulations, which may be of significant interest for understanding the kinetics of drug release.
Asunto(s)
Antibacterianos/química , Portadores de Fármacos/química , Composición de Medicamentos , Emulsiones/química , Gatifloxacina/química , 1-Butanol/química , Aceite de Clavo/química , Liberación de Fármacos , Glicol de Etileno/química , Tamaño de la Partícula , Transición de Fase , Polisorbatos/química , Solubilidad , Viscosidad , Agua/químicaRESUMEN
Various dressings are available to heal chronic wounds which many times fail to achieve the expected results. To overcome some of their drawbacks, formulation of a novel dressing; lyophilized liposomal wafers having better wound healing potential has been proposed in the present study. The drug incorporated in the formulation is gatifloxacin (GTX) which is a fourth-generation fluoroquinolone antibiotic having in vitro activity against both Gram-negative and Gram-positive bacteria. The formulation was designed in three stages where at first liposomes were prepared, the liposomes were converted to gel using chitosan and lastly this gel was lyophilized to form liposomal wafers. Liposomes were prepared by varying the concentration of lipid and cholesterol and evaluated for particle size, entrapment efficiency, in vitro cumulative release, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Liposomes were converted to liposomal gel using chitosan and evaluated for texture, clarity, viscosity, spreadibility and in vitro drug release. Finally, this liposomal batch was subjected to lyophilization to convert it to liposomal wafers and subjected to SEM, differential scanning calorimetric, X-ray diffraction and drug release studies. The in vivo studies were carried out on Wistar rats where wound healing potential of the wafers was confirmed by histopathological evaluation.