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Jeffrey J. Collins - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of oral Cefuroxime Axetil and oral amoxycillin/clavulanate in the treatment of community-acquired pneumonia
    2015
    Co-Authors: Jeffrey J. Collins
    Abstract:

    Cefuroxime Axetil has been evaluated previously in the treatment of lower respiratory tract infections, but not specifically in the treatment of community-acquired pneumonia. In a multicentre, investigator-blinded clinical trial, 162 patients with community-acquired pneumonia were randomly assigned to receive orally either Cefuroxime Axetil 500 mg bid (n = 84) or amoxycillin/clavulanate 500 mg/125 mg tid (n = 78) for 10 days. Organisms were isolated from the pretreatment sputum specimens of 97 of 162 (60%) patients, the commonest isolates being Streptococcus pneumoniae (38%) and Haemophilus influenzae (18%). A satisfactory clinical outcome (cure or improvement) was achieved in 100 % (55 of 55) and 96 % (49 of 51) of the clinically evaluable patients treated with Cefuroxime Axetil or amoxycillin/clavulanate, respectively (P = 0.23). With respect to eradication of bacterial pathogens, a satisfactory outcome (cure, presumed cure or cure with colonization) was obtained in 94 % (32 of 34) and 93 % (37 of 40) of bacteriologically evaluable patients treated with Cefuroxime Axetil or amoxycillin/clavulanate, respectively (P=1.00). Both treatment regimens used in this study were well tolerated. The most common drug-related adverse experiences were gastrointestinal events, reported by 8 % and 4%, respectively, of the patients in the amoxycillin/clavulanate and Cefuroxime Axetil groups, a difference which was not statistically significant (P = 0.32). These results indicate that Cefuroxime Axetil twice a day is as effective as amoxycillin/clavulanate three times a day in the treatment of outpatients with mild to moderate community-acquired pneumonia

  • clinical comparison of Cefuroxime Axetil and amoxicillin clavulanate in the treatment of patients with acute bacterial maxillary sinusitis
    The American Journal of Medicine, 1992
    Co-Authors: Alfonso E Camacho, Roxana Cobo, Jorge Otte, Sheldon L Spector, Charles Lerner, Norman Garrison, Aroldo Miniti, Patricia K Mydlow, Gregory Giguere, Jeffrey J. Collins
    Abstract:

    Purpose This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, Cefuroxime Axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis. Patients and methods Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with Cefuroxime Axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160). Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks). Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit. Results Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp. (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%). A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with Cefuroxime Axetil or amoxicillin/clavulanate, respectively (P = 0.446). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with Cefuroxime Axetil or amoxicillin/clavulanate, respectively (p = 0.567). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001). Two patients in the Cefuroxime Axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events. Conclusions Our results indicate that Cefuroxime Axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects.

  • comparison of Cefuroxime Axetil and doxycycline in the treatment of early lyme disease
    Annals of Internal Medicine, 1992
    Co-Authors: R B Nadelman, Jeffrey J. Collins, S W Luger, M Wisniewski, Elliot Frank, Gary P Wormser
    Abstract:

    Abstract ▪Objective:To compare the efficacy of Cefuroxime Axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. ▪Design:Randomized, multicenter, in...

Anant Paradkar - One of the best experts on this subject based on the ideXlab platform.

  • Cefuroxime Axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability
    Journal of Pharmacy and Pharmacology, 2009
    Co-Authors: Ravindra S Dhumal, Shailesh V Biradar, Suyog Aher, Anant Paradkar
    Abstract:

    Objectives Cefuroxime Axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Methods Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. Key findings SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Conclusions Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non-absorbable base form.

  • preparation of amorphous Cefuroxime Axetil nanoparticles by sonoprecipitation for enhancement of bioavailability
    European Journal of Pharmaceutics and Biopharmaceutics, 2008
    Co-Authors: Ravindra S Dhumal, Anant Paradkar, Shailesh V Biradar, Shigeo Yamamura, Peter York
    Abstract:

    The aim of the present work was to prepare amorphous discreet nanoparticles by sonoprecipitation method for enhancing oral bioavailability of Cefuroxime Axetil (CA), a poorly water-soluble drug. CA nanoparticles (SONO-CA) were prepared by sonoprecipitation and compared with particles obtained by precipitation without sonication (PPT-CA) and amorphous CA obtained by spray drying. Spray drying present broad particle size distribution (PSD) with mean particle size of 10 microm and low percent yield, whereas, precipitation without sonication resulted in large amorphous aggregates with broad PSD. During sonoprecipitation, particle size and yield improve with an increase in the amplitude of sonication and lowering the operation temperature due to instantaneous supersaturation and nucleation. The overall symmetry and purity of CA molecule was maintained as confirmed by FTIR and HPLC, respectively. All the three methods resulted in the formation of amorphous CA with only sonoprecipitation resulting in uniform sized nanoparticles. Sonoprecipitated CA nanoparticles showed enhanced dissolution rate and oral bioavailability in Wistar rat due to an increased solubility attributed to combination of effects like amorphization and nanonization with increased surface area and reduced diffusion pathway.

Fritz Sorgel - One of the best experts on this subject based on the ideXlab platform.

  • new semiphysiological absorption model to assess the pharmacodynamic profile of Cefuroxime Axetil using nonparametric and parametric population pharmacokinetics
    Antimicrobial Agents and Chemotherapy, 2009
    Co-Authors: Jurgen B Bulitta, Cornelia B Landersdorfer, Martina Kinzig, Ulrike Holzgrabe, Fritz Sorgel
    Abstract:

    Cefuroxime Axetil is widely used to treat respiratory tract infections. We are not aware of a population pharmacokinetic (PK) model for Cefuroxime Axetil. Our objectives were to develop a semiphysiological population PK model and evaluate the pharmacodynamic profile for Cefuroxime Axetil. Twenty-four healthy volunteers received 250 mg oral Cefuroxime as a suspension after a standardized breakfast. Liquid chromatography-tandem mass spectrometry was used for drug analysis, NONMEM and S-ADAPT (results reported) were used for parametric population PK modeling, and NPAG was used for nonparametric population PK modeling. Monte Carlo simulations were used to predict the duration for which the non-protein-bound-plasma concentration was above the MIC (fT>MIC). A model with one disposition compartment, a saturable and time-dependent drug release from the stomach, and fast drug absorption from the intestine yielded precise (r > 0.992) and unbiased curve fits and an excellent predictive performance. The apparent clearance was 21.7 liters/h (19.8% coefficient of variation [CV]) and the volume of distribution 38.7 liters (18.3% CV). Robust (≥90%) probabilities of target attainment (PTAs) were achieved by 250 mg Cefuroxime given every 12 h (q12h) or q8h for MICs of ≤0.375 mg/liter or ≤0.5 mg/liter, respectively, for the bacteriostasis target fT>MIC of ≥40% and for MICs of ≤0.094 mg/liter or ≤0.375 mg/liter, respectively, for the near-maximal-killing target fT>MIC of ≥65%. For the ≥40% fT>MIC target, the PTAs for 250 mg Cefuroxime q12h were ≥97.8% for Streptococcus pyogenes and penicillin-susceptible Streptococcus pneumoniae. Cefuroxime at 250 mg q12h or q8h achieved PTAs below 73% or 92%, respectively, for Haemophilus influenzae, Moraxella catarrhalis, and penicillin-intermediate S. pneumoniae for susceptibility data from various countries. Depending on the MIC distribution, 250 mg oral Cefuroxime q8h instead of q12h should be considered, especially for more-severe infections that require near-maximal killing by Cefuroxime.

  • new semiphysiological absorption model to assess the pharmacodynamic profile of Cefuroxime Axetil using nonparametric and parametric population pharmacokinetics
    Antimicrobial Agents and Chemotherapy, 2009
    Co-Authors: Jurgen B Bulitta, Cornelia B Landersdorfer, Martina Kinzig, Ulrike Holzgrabe, Fritz Sorgel
    Abstract:

    Cefuroxime Axetil is widely used to treat respiratory tract infections. We are not aware of a population pharmacokinetic (PK) model for Cefuroxime Axetil. Our objectives were to develop a semiphysiological population PK model and evaluate the pharmacodynamic profile for Cefuroxime Axetil. Twenty-four healthy volunteers received 250 mg oral Cefuroxime as a suspension after a standardized breakfast. Liquid chromatography-tandem mass spectrometry was used for drug analysis, NONMEM and S-ADAPT (results reported) were used for parametric population PK modeling, and NPAG was used for nonparametric population PK modeling. Monte Carlo simulations were used to predict the duration for which the non-protein-bound-plasma concentration was above the MIC (fT(>MIC)). A model with one disposition compartment, a saturable and time-dependent drug release from the stomach, and fast drug absorption from the intestine yielded precise (r > 0.992) and unbiased curve fits and an excellent predictive performance. The apparent clearance was 21.7 liters/h (19.8% coefficient of variation [CV]) and the volume of distribution 38.7 liters (18.3% CV). Robust (>or=90%) probabilities of target attainment (PTAs) were achieved by 250 mg Cefuroxime given every 12 h (q12h) or q8h for MICs of MIC) of >or=40% and for MICs of MIC) of >or=65%. For the >or=40% fT(>MIC) target, the PTAs for 250 mg Cefuroxime q12h were >or=97.8% for Streptococcus pyogenes and penicillin-susceptible Streptococcus pneumoniae. Cefuroxime at 250 mg q12h or q8h achieved PTAs below 73% or 92%, respectively, for Haemophilus influenzae, Moraxella catarrhalis, and penicillin-intermediate S. pneumoniae for susceptibility data from various countries. Depending on the MIC distribution, 250 mg oral Cefuroxime q8h instead of q12h should be considered, especially for more-severe infections that require near-maximal killing by Cefuroxime.

Jianfeng Chen - One of the best experts on this subject based on the ideXlab platform.

  • liquid antisolvent preparation of amorphous Cefuroxime Axetil nanoparticles in a tube in tube microchannel reactor
    International Journal of Pharmaceutics, 2010
    Co-Authors: Wenzhen Zhu, Jiexin Wang, Lei Shao, Haixia Zhang, Qianxia Zhang, Jianfeng Chen
    Abstract:

    Abstract This article presents the preparation of nanoparticles of amorphous Cefuroxime Axetil (CFA) in a microporous tube-in-tube microchannel reactor (MTMCR). The experimental results indicated that CFA particle with a tunable size of 400–1400 nm could be achieved under a high throughput in the range of 1.5–6 L/min. The average particle size decreased with increasing overall volumetric flow rate and decreasing CFA concentration, micropore size, and annular channel width. The produced CFA nanoparticles were characterized by SEM, XRD, FT-IR, DSC and a dissolution test, which indicated that the nanosized CFA was amorphous and exhibited higher dissolution rate compared to the raw CFA. The MTMCR might offer a general and facile pathway for mass production of the nanoparticles of hydrophobic pharmaceuticals thanks to its high throughput capacity and excellent micromixing performance.

  • microfluidic synthesis of amorphous Cefuroxime Axetil nanoparticles with size dependent and enhanced dissolution rate
    Chemical Engineering Journal, 2010
    Co-Authors: Jiexin Wang, Lei Shao, Qianxia Zhang, Yue Zhou, Jianfeng Chen
    Abstract:

    Abstract In this work, size-controllable nanoparticles of amorphous Cefuroxime Axetil (CFA), a poorly water-soluble drug, have been prepared in a Y-junction microchannel reactor (YMCR) by nanoprecipitation for enhancing dissolution rate of CFA. The effects of the operation parameters, such as flow rate of CFA acetone solution, antisolvent flow rate, overall flow rate, CFA concentration and precipitation temperature, on particle size and size distribution were experimentally investigated. The results indicated that the particle size obviously decreased from 1100 to 630 nm with decreasing the CFA solution flow rate from 16 to 2 mL/min, and decreased from 450 to 350 nm with the decreased temperature from 50 to 5 °C. However, with the increase of the antisolvent flow rate at a fixed CFA solution flow rate of 4 mL/min, the particle size obviously decreased from 1229 nm (20 mL/min) to 581 nm (60 mL/min), and then increased to 698 nm (80 mL/min). Also, the particle size firstly decreased and then increased with the increase of the overall flow rate and CFA solution concentration. The as-prepared CFA nanoparticles displayed a size-dependent and significantly enhanced dissolution property when compared to raw CFA and commercial spray-dried CFA. This work suggests that the continuous synthesis in a microfluidic reactor is a simple and economic way to prepare pharmaceutical nanoparticles with tunable sizes.

  • preparation and characterization of amorphous Cefuroxime Axetil drug nanoparticles with novel technology high gravity antisolvent precipitation
    Industrial & Engineering Chemistry Research, 2006
    Co-Authors: Jianfeng Chen, Jiyao Zhang, Zhigang Shen, And Jie Zhong, Jimmy Yun
    Abstract:

    Amorphous nanoparticles of Cefuroxime Axetil (CFA), a kind of poorly water-soluble antibiotic drug, were prepared at massive production rate by a novel continuous process, the high-gravity antisolvent precipitation (HGAP). The produced CFA nanoparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), powder X-ray diffraction (XRD), specific surface area analysis (BET), differential scanning calorimetry (DSC), and a dissolution test. The mean particle size of CFA was about 300 nm with a narrow distribution from 100 to 400 nm. The specific surface area reached up to 8.67 m2/g, which was about 4 times higher than that of the commercial spray-dried CFA. And the results of the dissolution test showed that dissolution rate of the former were higher than that of the latter. Hence it is proved the HGAP technique offers a direct and continuous process for mass-production of drug nanoparticles.

  • preparation of amorphous Cefuroxime Axetil nanoparticles by controlled nanoprecipitation method without surfactants
    International Journal of Pharmaceutics, 2006
    Co-Authors: Jiyao Zhang, Zhigang Shen, Jie Zhong, Jianfeng Chen, Jimmy Yun
    Abstract:

    Abstract Amorphous nanoparticles of Cefuroxime Axetil (CFA), a poorly water-soluble drug, were produced by the controlled nanoprecipitation method without any surfactants at room temperature. The influence of the operation parameters, such as the types of solvent and anti-solvent, the stirring speed, the solvent/anti-solvent (S/AS) volume ratio, the drug concentration and the precipitation temperature, were experimentally investigated. The results indicated that increasing the stirring speed and the S/AS volume, decreasing the drug concentration and the temperature favored to decrease the particle size from 700 to 900 nm to ∼300 nm. The XRD analyses confirmed that the as-prepared CFA was amorphous nanoparticles. Furthermore, the amorphous CFA nanoparticles exhibited significantly enhanced dissolution property when compared to the commercial spray-dried product. The results demonstrated that the controlled nanoprecipitation method is a direct and feasible technology which could be utilized for preparation of the poorly water-soluble pharmaceutical nanoparticles.

Ravindra S Dhumal - One of the best experts on this subject based on the ideXlab platform.

  • Cefuroxime Axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability
    Journal of Pharmacy and Pharmacology, 2009
    Co-Authors: Ravindra S Dhumal, Shailesh V Biradar, Suyog Aher, Anant Paradkar
    Abstract:

    Objectives Cefuroxime Axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Methods Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. Key findings SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Conclusions Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non-absorbable base form.

  • preparation of amorphous Cefuroxime Axetil nanoparticles by sonoprecipitation for enhancement of bioavailability
    European Journal of Pharmaceutics and Biopharmaceutics, 2008
    Co-Authors: Ravindra S Dhumal, Anant Paradkar, Shailesh V Biradar, Shigeo Yamamura, Peter York
    Abstract:

    The aim of the present work was to prepare amorphous discreet nanoparticles by sonoprecipitation method for enhancing oral bioavailability of Cefuroxime Axetil (CA), a poorly water-soluble drug. CA nanoparticles (SONO-CA) were prepared by sonoprecipitation and compared with particles obtained by precipitation without sonication (PPT-CA) and amorphous CA obtained by spray drying. Spray drying present broad particle size distribution (PSD) with mean particle size of 10 microm and low percent yield, whereas, precipitation without sonication resulted in large amorphous aggregates with broad PSD. During sonoprecipitation, particle size and yield improve with an increase in the amplitude of sonication and lowering the operation temperature due to instantaneous supersaturation and nucleation. The overall symmetry and purity of CA molecule was maintained as confirmed by FTIR and HPLC, respectively. All the three methods resulted in the formation of amorphous CA with only sonoprecipitation resulting in uniform sized nanoparticles. Sonoprecipitated CA nanoparticles showed enhanced dissolution rate and oral bioavailability in Wistar rat due to an increased solubility attributed to combination of effects like amorphization and nanonization with increased surface area and reduced diffusion pathway.

  • design and evaluation of bilayer floating tablets of Cefuroxime Axetil for bimodal release
    Journal of Scientific & Industrial Research, 2006
    Co-Authors: Ravindra S Dhumal, Samitkumar T Rajmane, Sanjay T Dhumal, Atmaram Pawar
    Abstract:

    Study aims to design a gastroretentive delivery system for bimodal release of Cefuroxime Axetil (CA). CA has site-specific absorption from upper gastrointestinal tract and in intestine it undergoes hydrolysis to Cefuroxime having poor absorption. Unabsorbed drug causes high concentration of antibiotic entering colon and contributes to the side effects like colitis. Therefore, a gastro-retentive dosage form is required to ensure controlled drug delivery within drug-absorbable regions. Bilayer tablet, each layer containing half the dose of drug was formulated with one immediate release layer (IRL) and another floating matrix layer (FML). The FML showed good floating properties with buoyancy lag time of 12-35 min and floating time of 8-24 h. Thus, bimodal drug release comprising of immediate release for quick onset of action followed by controlled release minimizing the concentration of unabsorbed drug entering colon was achieved. No change in amorphous nature of drug during processing was observed, which was confirmed by differential scanning colorimeter and X-ray diffractometer. The y -sintigraphy confirmed the gastric residence of tablets in human volunteers.