RESUMO
The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.
Assuntos
Antibacterianos , Estabilidade de Medicamentos , Emulsões , Soluções Oftálmicas , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacocinética , Emulsões/química , Soluções Oftálmicas/química , Hidrólise , Óleo de Rícino/química , Cefuroxima/química , Cefuroxima/administração & dosagem , Cefuroxima/farmacocinética , Vancomicina/química , Vancomicina/administração & dosagem , Tensoativos/química , Química Farmacêutica/métodos , Suspensões , Água/química , Solubilidade , Polissorbatos/química , Azeite de Oliva/química , Hexoses/química , Portadores de Fármacos/químicaRESUMO
In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic ß-lactam antibiotics and ß-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g-1. The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 - 0.2 ng mL-1. In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3-105.4 % for intra-day and 90.6-103.5 % for inter-day, with low relative standard deviations of 1.3-7.2 % and 4.9-10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration.
Assuntos
Cefoperazona , Cefuroxima , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Nanotubos , Dióxido de Silício , Extração em Fase Sólida , Sulbactam , Cefoperazona/sangue , Cefoperazona/química , Humanos , Sulbactam/sangue , Sulbactam/química , Extração em Fase Sólida/métodos , Dióxido de Silício/química , Nanotubos/química , Cefuroxima/sangue , Cefuroxima/química , Argila/química , Adsorção , Antibacterianos/sangue , Antibacterianos/química , Polietilenoimina/química , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos TestesRESUMO
Environmental conditions can lead to changes in the physical and chemical structures of drug products. In this study, the stability of cefuroxime tablets stored under adverse conditions was evaluated based on total directional-hemispherical reflectance (THR). The THR value was measured before and after the tablets' exposure to stress factors (temperature of 45 °C and UV radiation). Each measurement was performed three times within seven spectral bands at the beginning of the experiment (day 0), and then on days 1, 2, 3, 5, and 7. In addition, hyperspectral profiles (400-1030 nm) were analyzed on days 0 and 7. A significant decrease in THR values in all wavelength ranges was observed when day 7 vs. day 0 were compared, especially for spectral bands of 335-380 nm and 1700-2500 nm (Δ = 0.220, p < 0.001 and Δ = 0.171, p < 0.001, respectively). The hyperspectral analysis confirmed a decrease in the reflectance after the end of stress conditions in the visible light range (400-700 nm) compared to tablets before the experiment. This may indicate that more radiation entered the tablets. In conclusion, the THR of cefuroxime tablets decreases during the exposure to heat and UV radiation, which may result from some physicochemical changes that have occurred during storage.
Assuntos
Cefuroxima , Raios Ultravioleta , Cefuroxima/química , Temperatura , Luz , ComprimidosRESUMO
Dental caries results from the bacterial pathogen Streptococcus mutans (S. mutans) and is the maximum critical reason for caries formation. Consequently, the present study aims to evaluate the antibacterial activity of a newly synthesized nanoantibiotic-Biodentine formulation. The silver nanoparticles (ROE-AgNPs) were biosynthesized from the usage of Rosmarinus officinalis L. extract (ROE) and conjugated with cefuroxime to form Cefuroxime-ROE-AgNPs. Using Biodentine™ (BIOD), five groups of dental materials were prepared, in which Group A included conventional BIOD, Group B included BIOD with ROE-AgNPs, Groups C and D included BIOD with Cefuroxime-ROE-AgNPs at concentrations of 0.5% and 1.5% cefuroxime, respectively, and Group E included BIOD with 1.5% cefuroxime. The synthesized ROE-AgNPs or Cefuroxime-ROE-AgNPs were characterized for conjugating efficiency, morphology, particle size, and in vitro release. Minimum inhibitory concentration (MIC) of the cefuroxime, ROE-AgNPs, and Cefuroxime-ROE-AgNPs were additionally evaluated against cefuroxime resistant S. mutans, which furthered antibacterial efficacy of the five groups of dental materials. The UV-Visible spectrum showed the ROE-AgNPs or Cefuroxime-ROE-AgNPs peaks and their formation displayed through transmission electron microscopy (TEM), X-ray diffraction (XRD) pattern, and Fourier transforms infrared (FTIR) analysis. The end result of Cefuroxime-ROE-AgNPs showed conjugating efficiency up to 79%. Cefuroxime-ROE-AgNPs displayed the highest antibacterial efficacy against S. mutans as compared to cefuroxime or ROE-AgNPs alone. Moreover, the MIC of ROE-AgNPs and Cefuroxime-ROE-AgNPs was detected against S. mutans to be 25 and 8.5 µg/mL, respectively. Consequently, Cefuroxime-ROE-AgNPs displayed that a decrease in the MIC reached to more than three-fold less than MIC of ROE-AgNPs on the tested strain. Moreover, Cefuroxime-ROE-AgNPs/BIOD was employed as a novel dental material that showed maximum antimicrobial activity. Groups C and D of novel materials showed inhibitory zones of 19 and 26 mm, respectively, against S. mutans and showed high antimicrobial rates of 85.78% and 91.17%, respectively. These data reinforce the utility of conjugating cefuroxime with ROE-AgNPs to retrieve its efficiency against resistant S. mutant. Moreover, the nanoantibiotic delivered an advantageous antibacterial effect to BIOD, and this may open the door for future conjugation therapy of dental materials against bacteria that cause dental caries.
Assuntos
Compostos de Cálcio/química , Compostos de Cálcio/farmacologia , Cefuroxima/química , Cefuroxima/farmacologia , Nanopartículas Metálicas/química , Silicatos/química , Silicatos/farmacologia , Prata/química , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Cárie Dentária/tratamento farmacológico , Testes de Sensibilidade Microbiana/métodos , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
The formation of cefuroxime axetil+cyclodextrin (CA+CD) complexes increases the aqueous solubility of CA, improves its physico-chemical properties, and facilitates a biomembrane-mediated drug delivery process. In CD-based tablet formulations, it is crucial to investigate the molecular details of complexes in final pharmaceutical preparation. In this study, Raman spectroscopy and mapping were applied for the detection and identification of chemical groups involved in α-, ß-, γ-, and 2-hydroxypropyl-ß-CD (2-HP- ß-CD)+CA complexation process. The experimental studies have been complemented by molecular dynamics-based investigations, providing additional molecular details of CA+CD interactions. It has been demonstrated that CA forms the guest-host type inclusion complexes with all studied CDs; however, the nature of the interactions is slightly different. It seems that both α- and ß-CD interact with furanyl and methoxy moieties of CA, γ-CD forms a more diverse pattern of interactions with CA, which are not observed in other CDs, whereas 2HP-ß-CD binds CA with the contribution of hydrogen bonding. Apart from supporting this interpretation of the experimental data, molecular dynamics simulations allowed for ordering the CA+CD binding affinities. The obtained results proved that the molecular details of the host-guest complexation can be successfully predicted from the combination of Raman spectroscopy and molecular modeling.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina , Cefuroxima/análogos & derivados , Ciclodextrinas/química , Análise Espectral Raman , 2-Hidroxipropil-beta-Ciclodextrina/química , Cefuroxima/química , Ligação de Hidrogênio , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , VibraçãoRESUMO
Cefuroxime (CFX) is a broad-spectrum second-generation cephalosporin and one of the best choices for antibiotic prophylaxis. However, when used in critically ill patients, it may present changes in its pharmacokinetic properties. Therefore, therapeutic drug monitoring of CFX is necessary for effective dosing strategies. A simple, rapid and sensitive liquid chromatographic method with UV detection was developed and validated for the quantification of CFX in plasma. The method involved a single-step precipitation of proteins with methanol and trifluoroacetic acid. Cefuroxime was analyzed on a Brisa LC2 C18 column in isocratic mode consisting of 0.1% trifluoroacetic acid in water and acetonitrile (75:25) with UV detection at a wavelength of 280 nm. The retention times of CFX and cephazolin (internal standard) were 9.8 and 7.4 min, respectively. The calibration curve was linear over a concentration range of 0.25-50 µg/ml. The limits of detection and quantification were 0.1 µg/ml and 0.25 µg/ml, respectively. The accuracy and precision were always <10%. The mean recovery was 93.52%. This fast and simple method could be applied in routine analysis and pharmacokinetic studies.
Assuntos
Cefuroxima/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrofotometria Ultravioleta/métodos , Cefuroxima/química , Cefuroxima/farmacocinética , Monitoramento de Medicamentos , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos TestesRESUMO
New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for ß-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty ß-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-ß-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-ß-lactam IgE antibodies with high sensitivity (< 0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of ß-lactam antibiotics renders improved molecular recognition events when the 4-member ß-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.
Assuntos
Hipersensibilidade a Drogas/imunologia , beta-Lactamas/imunologia , Antibacterianos/imunologia , Aztreonam/química , Aztreonam/imunologia , Carbapenêmicos/imunologia , Carbapenêmicos/farmacologia , Cefotaxima/química , Cefotaxima/imunologia , Ceftriaxona/química , Ceftriaxona/imunologia , Cefuroxima/química , Cefuroxima/imunologia , Cefalosporinas/imunologia , Cefalosporinas/farmacologia , Reações Cruzadas , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Meropeném/química , Meropeném/imunologia , Monobactamas/imunologia , Monobactamas/farmacologia , Penicilinas/imunologia , Testes CutâneosAssuntos
Anafilaxia/induzido quimicamente , Antibacterianos/efeitos adversos , Cefuroxima/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Adolescente , Anafilaxia/imunologia , Antibacterianos/química , Antibacterianos/imunologia , Cefuroxima/química , Cefuroxima/imunologia , Cefalosporinas/química , Cefalosporinas/imunologia , Reações Cruzadas/imunologia , Feminino , HumanosRESUMO
The anodized titanium nanotubes (TiO2-NTs) are considered to be a potential material in clinical therapy. To enhance the antibacterial property of TiO2-NTs, cefuroxime is introduced into TiO2-NTs, and then, different chitosan layers are coated to control the release of cefuroxime. SEM and FTIR are adapted for the characterization of prepared TiO2-NTs. The effects of chitosan coating thickness on release of cefuroxime are also investigated, followed with the antibacterial property evaluation. The results show TiO2-NTs are fabricated by anodization method and cefuroxime is also successfully loaded into the nanotubes. The thickness of chitosan coating is an important factor to the release rate of cefuroxime. Antimicrobial detection and morphology observation of S. aureus show a sustained 7-day drug release and strong negative effect on bacteria. The approach in this study provides a broadly applicable method to fabricate titanium-based orthopedic implants with enhanced antibacterial properties.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Cefuroxima/química , Nanotubos/química , Titânio/química , Antibacterianos/química , Bactérias/efeitos dos fármacos , Cefuroxima/farmacologia , Quitosana/química , Materiais Revestidos Biocompatíveis/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Propriedades de Superfície , Titânio/farmacologiaRESUMO
This study aimed to investigate changes in the solubility and antimicrobial efficacy of cefuroxime axetil (CA) when incorporated into cyclodextrin (CD). While choosing the CD, the validated in silico model was used. A theoretical model based on docking and molecular mechanics/generalized born surface area was validated using a curated dataset of API (active pharmaceutical ingredient)-CD stability constants. The library of commonly used cyclodextrins was virtually screened, indicating CA -hydroxypropyl-ßCD (HPßCD) as the most thermodynamically favored system. Solid-state CA-HPßCD system was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRPD) methods. The dissolution profiles of the CA and its cyclodextrin system were evaluated. Microbiological activity of the CA-HPßCD inclusion system was studied based on changes in minimal inhibitory concentration (MIC) values and related to ones of the pure CA. The theoretical model was successfully validated, obtaining an average correlation with experimental data R = 0.7. The dissolution study showed significantly improved dissolution profiles of CA-HPßCD compared to CA. HPßCD increases the antimicrobial efficacy of CA up to 4-fold compared to pure CA.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Cefuroxima/análogos & derivados , Desenho Assistido por Computador , Ciclodextrinas/química , Cefuroxima/química , Cefuroxima/farmacologia , Simulação por Computador , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Solubilidade , Relação Estrutura-AtividadeRESUMO
Cefuroxime Axetil (CA) is a poorly soluble, broad spectrum antibiotic which undergoes enzymatic degradation in gastrointestinal tract. The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery systems containing CA using hot-melt extrusion (HME) to improve absorption. Selected formulations of CA and lipids were extruded using a twin screw hot-melt extruder. Milled extrudates were characterized for dissolution, floating strength, and micromeritic properties. Solid-state characterization was performed using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and hot-stage microscopy. In vitro characterization demonstrated that the formulations exhibited a sustained drug release profile for 12â¯h. All formulations showed desired floating and flow properties. Solid-state characterization revealed no phase separation and no chemical interactions between the drug and excipients. Based on in vitro study results, an optimized formulation (F8) was further evaluated for in vivo performance. Oral bioavailability (Cmax and AUC0-24h) of F8 was significantly higher than that of pure CA. This study describes the use of lipid-based gastro-retentive floating drug delivery systems to achieve desired sustained release profile for more complete dissolution which could potentially reduce enzymatic degradation. This study also highlights the effectiveness of HME technology to improve dissolution and bioavailability.
Assuntos
Antibacterianos/administração & dosagem , Cefuroxima/análogos & derivados , Sistemas de Liberação de Medicamentos , Administração Oral , Animais , Antibacterianos/sangue , Antibacterianos/química , Antibacterianos/farmacocinética , Disponibilidade Biológica , Cefuroxima/administração & dosagem , Cefuroxima/sangue , Cefuroxima/química , Cefuroxima/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Tecnologia de Extrusão por Fusão a Quente , Masculino , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Ratos Sprague-Dawley , Estômago/fisiologiaRESUMO
The aim of the present investigation was to improve the compressibility and flow property of cefuroxime axetil by co-processing it with mannitol and chitosan chlorhydrate using spray drying method. 32 full factorial design, having inlet air temperature and mannitol: chitosan chlorhydrate ratio as independent variables was used for the optimization. Statistical analysis of obtained results revealed that both independent variables had significant effect on response variables (p value < .05). Evaluation of dependent variables suggested, excellent to good flow properties (angle of repose, Carr's index, and Hausner's ratio) for all prepared batches. Desirability function was used for the selection of the optimized batch which was evaluated for Kawakita's equation, Heckel's plot to assess compression behavior of co-processed product under applied pressure. Result of this analysis revealed that the optimized batch product had better compressibility than physical mixture. The tablets prepared by directly compressing spray-dried product, exhibited excellent tensile strength acceptable friability (<1%) and similar release profile when compared with marketed formulation (Similarity factor 89.24 and dissimilarity factor 1.79). So the results of the present investigation concluded that cefuroxime axetil was successfully co-processed with above mentioned excipients by using spray drying method to make it directly compressible.
Assuntos
Cefuroxima/análogos & derivados , Composição de Medicamentos/métodos , Excipientes/química , Cefuroxima/química , Química Farmacêutica/métodos , Quitosana/química , Dessecação/métodos , Pós , ComprimidosRESUMO
The aim of this study is to investigate the dissolution properties of poorly soluble drugs from their pure form and their amorphous formulation under physiological relevant conditions for oral administration based on surface dissolution ultraviolet (UV) imaging. Dissolution of two poorly soluble drugs (cefuroxime axetil and itraconazole) and their amorphous formulations (Zinnat® and Sporanox®) was studied with the Sirius Surface Dissolution Imager (SDI). Media simulating the fasted state conditions (compendial and biorelevant) with sequential media/flow rate change were used. The dissolution mechanism of cefuroxime axetil in simulated gastric fluid (SGF), fasted state simulated gastric fluid (FaSSGF) and simulated intestinal fluid (SIF) is predominantly swelling as opposed to the convective flow in fasted state simulated intestinal fluid (FaSSIF-V1), attributed to the effect of mixed micelles. For the itraconazole compact in biorelevant media, a clear upward diffusion of the dissolved itraconazole into the bulk buffer solution is observed. Dissolution of itraconazole from the Sporanox® compact is affected by the polyethylene glycol (PEG) gelling layer and hydroxypropyl methylcellulose (HPMC) matrix, and a steady diffusional dissolution pattern is revealed. A visual representation and a quantitative assessment of dissolution properties of poorly soluble compounds and their amorphous formulation can be obtained with the use of surface dissolution imaging under in vivo relevant conditions.
Assuntos
Antibacterianos/química , Antifúngicos/química , Cefuroxima/análogos & derivados , Composição de Medicamentos , Itraconazol/química , Espectrofotometria Ultravioleta/métodos , Líquidos Corporais , Cefuroxima/química , Micelas , Solubilidade , Propriedades de SuperfícieRESUMO
The presence of unwanted competing flora has been the most common confounding factor in the enumeration of Bacillus cereus (B. cereus) using selective media such as mannitol-yolk-polymyxin B agar (MYPA). The objective of this study was to improve MYPA selectivity for B. cereus by supplementation with a second-generation cephalosporin, cefuroxime. The performance of cefuroxime-supplemented MYPA (cefu-MYPA) was evaluated by comparison with original MYPA in 60 food products with established microbiological standards for B. cereus contamination. Cefu-MYPA demonstrated superior recoverability and selectivity for B. cereus compared with original MYPA in most tested foods. B. cereus numbers on MYPA and cefu-MYPA were 363.5 and 462.0 CFU/g, respectively. Competing flora on cefu-MYPA was detected in significantly less samples (70%) compared to original MYPA (93%). In addition, the detection and isolation of suspected colonies were significantly improved in cefu-MYPA because of the reduction or elimination of competing flora in all tested foods except fruit juice, indicating superior selectivity of the modified medium. Our findings suggest that cefuroxime supplementation of MYPA would markedly improve the detection rate of B. cereus, particularly in foods with high levels of indigenous flora.
Assuntos
Bacillus cereus/isolamento & purificação , Cefuroxima/química , Meios de Cultura/química , Gema de Ovo/química , Contaminação de Alimentos/análise , Manitol/química , Ágar/química , Contagem de Colônia Microbiana , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana , Polimixina B/químicaRESUMO
Hydrogels are excellent drug delivery systems for the treatment of chronic wound infections. However, the problem of high burst release still remains a challenge that needs to be tackled. In terms of antibiotic release from the hydrogels, as the drug payload depletes it could act as a substrate for bacterial seeding which can create a life-threatening condition. Therefore, to provide the sustained effect of an antibiotic at the localized site via hydrogel matrix, we prepared a chitosan (CS) hydrogel system in which cefuroxime (CEF) is covalently conjugated with chitosan polymer via an ester linkage. To prepare the cefuroxime conjugated chitosan hydrogel, the formulations were optimized using different concentrations of cefuroxime, 0% (CS/CEF_0), 5% (CS/CEF_5), 10% (CS/CEF_10) and 20% (CS/CEF_20) w/w of chitosan. Fourier Transform Infra-red Spectroscopy (FTIR) confirmed the conjugation of cefuroxime and chitosan. The drug release studies showed that the release of cefuroxime was higher in the phosphate buffer (pH 7.4) with esterase enzyme and alkaline medium (pH 10) compared to phosphate buffer (pH 7.4) alone. Hemolysis assay was performed to demonstrate the hemocompatibility of the prepared hydrogel samples. The cell viability study using the L929 fibroblast and MG63 osteosarcoma cell lines revealed that synthesized hydrogel is biocompatible. Furthermore, a potent antibacterial activity for the extended time period proved the biological efficacy of a hydrolyzed cefuroxime. Thus, CS/CEF_5, CS/CEF_10, and CS/CEF_20 hydrogels have a promising future in the treatment of chronic wound infections.
Assuntos
Antibacterianos/química , Cefuroxima/química , Quitosana/química , Preparações de Ação Retardada , Glicoconjugados/química , Animais , Antibacterianos/farmacologia , Soluções Tampão , Cefuroxima/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Glicoconjugados/farmacologia , Hemólise/efeitos dos fármacos , Humanos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Cinética , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Infecção da Ferida Cirúrgica/terapiaAssuntos
Alérgenos/imunologia , Antibacterianos/imunologia , Cefuroxima/imunologia , Hipersensibilidade a Drogas/diagnóstico , Síndrome de Kounis/diagnóstico , Antibacterianos/química , Cefuroxima/química , Vasoespasmo Coronário , Reações Cruzadas , Dispneia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Infarto do Miocárdio , Distúrbios do PaladarRESUMO
CONTEXT: Cephalosporins are derived from the fungus Acremonium. Due to their strong bactericidal ability, these drugs have to a wide usage in medicine. OBJECTIVE: An investigation of the effects on sheep renal aldose reductase (AR) and sorbitol dehydrogenase (SDH) of cefoperazone, cefazolin, cefuroxime, ceftazidime and ceftriaxone as cephalosporin drugs was carried out in the present study. METHODS: AR and SDH were purified from sheep kidney by ion exchange, gel filtration and affinity methods with approximately 219- and 484-fold, respectively. Some kinetic properties of the enzymes were determined such as optimal pH, optimal ionic strength, optimal temperature, stable pH, Km and Vmax. IC50 values of the drugs were found for each enzyme. RESULTS: While the AR was inhibited by all drugs, SDH enzyme was inhibited by only CXM (IC50 8.10 mM). Interestingly, CZO activated SDH enzyme. This result was evaluated as important for the flow of the polyol reactions. Ki values and inhibition types were determined for AR. However, these values could not have determined for SDH, due to insufficient inhibition. CONCLUSIONS: From these results, it was concluded that cephalosporins may have an important effect on flow of the polyol metabolism.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Inibidores Enzimáticos/farmacologia , Rim/enzimologia , L-Iditol 2-Desidrogenase/antagonistas & inibidores , Modelos Moleculares , Aldeído Redutase/isolamento & purificação , Aldeído Redutase/metabolismo , Animais , Antibacterianos/química , Cefazolina/química , Cefazolina/farmacologia , Cefoperazona/química , Cefoperazona/farmacologia , Ceftazidima/química , Ceftazidima/farmacologia , Ceftriaxona/química , Ceftriaxona/farmacologia , Cefuroxima/química , Cefuroxima/farmacologia , Cefalosporinas/química , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Gliceraldeído/metabolismo , Concentração de Íons de Hidrogênio , Cinética , L-Iditol 2-Desidrogenase/química , L-Iditol 2-Desidrogenase/isolamento & purificação , L-Iditol 2-Desidrogenase/metabolismo , Ovinos , Sorbitol/metabolismo , TemperaturaRESUMO
Cefuroxime axetil (CFA), an ester prodrug of cefuroxime exists as a pair of diastereoemers, namely isomer A and isomer B. To enable phase diagram construction, crystallization of the diastereomers of CFA from the commercially available amorphous drug substance was carried out. Isomer A was separated with a purity approaching 100% whereas the maximum purity of isomer B was 85% as confirmed by solution state proton NMR spectroscopy. The crystalline forms of isomer A and isomer B were confirmed as forms AI and BI, respectively, based on differential scanning calorimetry (DSC) analysis and powder X-ray diffraction. DSC analysis was used to observe the melting behavior of different diastereomer mixture compositions. The binary solid-liquid phase diagram for mixture compositions ranging from 0 to 85% w/w isomer B indicated the formation of a eutectic mixture having a melting temperature of 124.7 ± 0.4°C and a composition of 75% w/w (+/-5% wt.) isomer B. The eutectic composition was calculated using an index based on the van't Hoff equation for melting point depression and was found to be 75% isomer B and 25% isomer A. As CFA is present in commercial preparations as a mixture of diastereomers, the formation of a eutectic mixture between the diastereomers may impact the solubility and stability of the commercial product. Eutectic formation can be explained on the basis of the chemical similarity of diastereomers that favor miscibility in the liquid state.
Assuntos
Cefuroxima/análogos & derivados , Cefuroxima/química , Cristalização , Solubilidade , Estereoisomerismo , TemperaturaRESUMO
CONTEXT: Injecting intracameral cefuroxime has been found beneficial in reducing the risk of postoperative endophthalmitis but its use has been limited through a lack of approved marketing and of ready-to-use single-units as well as the problem of aseptic compounding. OBJECTIVE: Our aim was to assess a new automated primary packaging system which should ensure a higher level of sterility, thanks to its closed, sterile, ready-to-use polymer vial called "Crystal® vial". The chemical stability of a 10 mg/mL cefuroxime solution was compared in 1 mL Crystal® vials and 1 mL Luer-lock polypropylene syringes (actual reference) to eliminate any potential and specific interactions with its cyclic olefin copolymer (COC) body and elastomer stopper. METHODS: Cefuroxime solution was introduced into vials and syringes and stored at -20 °C, +5 °C and +25°C/60% Relative Humidity. Cefuroxime concentration and the relative amount of the main degradation product (descarbamoyl-cefuroxime) were both determined by an HPLC/UV method indicating stability. Solutions were considered steady if the concentration remained at over 90% of the initial value. In the adapted storage conditions, the evolution of osmolality, pH and sterility was assessed. RESULTS: Stability profiles were identical between vials and syringes in all storage and temperature conditions. The solution was stable (cefuroxime concentration, pH and osmolality) and still sterile for 365 days at -20°C. The concentration fell below 90% after 21 days at +5 °C and after 16 h at +25°C/60%s relative humidity. CONCLUSIONS: The COC and thermoplastic elastomer of the vials had no impact on the degradation process confirming its possible use for a ready-to-use cefuroxime solution single-unit dose.
Assuntos
Cefuroxima/química , Cicloparafinas/química , Embalagem de Medicamentos/métodos , Polipropilenos/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/uso terapêutico , Cefuroxima/administração & dosagem , Cefuroxima/uso terapêutico , Composição de Medicamentos/normas , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Endoftalmite/prevenção & controle , Estudos de Viabilidade , Vidro , Injeções Intraoculares , Concentração Osmolar , Soluções Farmacêuticas/administração & dosagem , Soluções Farmacêuticas/química , Soluções Farmacêuticas/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Seringas , TemperaturaRESUMO
The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.