The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil(CFA), were prepared with β-cyclodextrin(βCD) with or without addition of L-arginine(ARG) to improve its physicochemical properties. We...The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil(CFA), were prepared with β-cyclodextrin(βCD) with or without addition of L-arginine(ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency(CE) of βCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL(linear) type of solubility curve in presence and absence of ARG, the CE and association constant(Ks) of βCD towards CFA were significantly promoted in presence of ARG,justifying its use as a ternary component. The solid systems of CFA with βCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning calorimetry(DSC), X-ray powder diffractometry(XRPD), scanning electron microscopy(SEM), and saturation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA inside βCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation with βCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclusion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA via βCD complexation.展开更多
Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared...Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared by means of wet granulation method and solid dispersion method.Binders,suspending agents and other compositions involved in the formulation were optimized.The differential scanning calorimetry(DSC)analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier,which contributed to an improvement of the dissolution rate.Taste evaluation was performed by three volunteers and taste masking was successfully achieved by the methods mentioned above.A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations,i.e.,two self-made dry suspensions and the commercial one.With a better release characteristic and a satisfying taste masking ability,the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs.The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension,respectively.The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability.展开更多
The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR spectroscopy to study the possible drug-drug or drug-excipient (s) interaction in case of concomitant oral administration...The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR spectroscopy to study the possible drug-drug or drug-excipient (s) interaction in case of concomitant oral administration of paracetamol with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime axetil and their commercially available suspensions, Amoxil?, Azithromax? and Zinnat? were used. DSC curves for paracetamol, pure antibiotics, commercially available antibiotics and all binary mixtures used in this study showed drug-drug or drug-excipient (s) physical interaction and indicated a possible chemical interaction. To confirm chemical drug-drug or drug-excipient (s) interaction additional ATR-IR spectra for all samples used in this study were obtained. Results obtained from ATR-IR spectra showed drug-excipient (s) interaction in Zinnat?, Azithromax? and binary mixture Azithromax?-paracetamol, while chemical drug-drug interaction was not observed. From this study it can be concluded that the concomitant oral administration of paracetamol with commercially available antibiotics used in this study is not recommended and duration of two hours between the oral administrations of these drugs is strongly recommended to avoid drug-drug or drug-excipient (s) interaction.展开更多
Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therape...Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.展开更多
This investigation was undertaken to enhance the solubility and consequent antibacterial activity of cefuroxime axetil (CA), a </span><i><span style="font-family:Verdana;">β</span>&l...This investigation was undertaken to enhance the solubility and consequent antibacterial activity of cefuroxime axetil (CA), a </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-lactamase-stable broad spectrum second generation cephalosporin through solid dispersion (SD) technique. For this purpose, CA loaded SDs (CSDs) were prepared by solvent evaporation method using different concentrations of microcrystalline cellulose (MCC) as carrier. The CSDs were characterized by </span><i><span style="font-family:Verdana;">in-vitro</span></i><span style="font-family:Verdana;"> dissolution study, thermal analysis (DSC), crystallinity (PXRD), interactions (FTIR) and morphology (SEM). Among the formulations, CSD-2 showed the highest dissolution rate which was 2.59-fold higher than pure CA with a drug-carrier (CA: MCC) ratio of 1:3. Enhanced dissolution rate was attributed to conversion of drug from crystalline to amorphous state during preparation of SDs, which was validated by DSC, PXRD, FTIR and SEM analyses. Antibacterial activity of CSD-2 against </span><i><span style="font-family:Verdana;">Staphylococcus aureus</span></i><span style="font-family:Verdana;"> (ATCC 25923) and </span><i><span style="font-family:Verdana;">Escherichia coli</span></i><span style="font-family:Verdana;"> (ATCC 25922) showed 1.94- and 6.75-fold higher relative zone of inhibition (RZOI), respectively than pure CA. CSD-2 has been found to be the most effective optimized formulation in terms of both enhanced dissolution rate and antibacterial activity. Thus, it can be an effective alternative to conventional dosage forms of CA. However, further investigations are needed to validate its pharmacokinetic properties, </span><i><span style="font-family:Verdana;">in-vivo </span></i><span style="font-family:Verdana;">antibacterial efficacy and safety before recommending as a novel展开更多
Objective: To investigate the effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity. Methods: Patients who underwent knee replace...Objective: To investigate the effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity. Methods: Patients who underwent knee replacement in People's Hospital of Dongxihu District between April 2015 and January 2018 were selected as the research subjects and randomly divided into the experimental group who accepted flurbiprofen axetil combined with patient-controlled intravenous analgesia and the control group who accepted patient-controlled intravenous analgesia alone. The contents of cytokines and HPA axis-related hormones in serum were measured before surgery as well as 1 d and 3 d after surgery;the contents of cytokines in joint fluid were measured 1 d and 3 d after surgery. Results: Compared with those of same group before surgery, NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels of both groups were increasing 1 d and 3 d after surgery, and NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels in serum as well as PGE2, OPN, TGF-β1, FGF21, CXCL12 and YKL-40 in joint fluid of experimental group 1 d and 3 d after surgery were lower than those of control group. Conclusion: Flurbiprofen axetil analgesia after knee replacement can reduce the release of cytokines in serum and joint fluid, and inhibit the activity of HPA axis, and its analgesic effect is exact.展开更多
Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underw...Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underwent operative treatment of femoral neck fracture in Guangyuan Hospital of Traditional Chinese Medicine between March 2014 and December 2017 were selected as the research subjects. All patients were randomly divided into the experimental group who accepted flurbiprofen axetil intervention before induction + routine anesthesia induction and maintenance, and the control group who accepted routine anesthesia induction and maintenance, and each group included 43 cases. The pain levels of the two groups were assessed 24 h after surgery;the levels of pain mediators and inflammatory stress molecules in serum as well as the expression intensity of inflammatory stress molecules in peripheral blood were determined before surgery and 24 h after surgery.Results:24 h after surgery, serum SP, NPY, PGE2, TNF-α, IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of both groups were significantly higher than those before surgery, and NRS pain score, serum SP, NPY, PGE2, TNF- , IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of experimental group 24 h after surgery were significantly lower than those of control group.Conclusions:Flurbiprofen axetil intervention before induction can improve and inhibit the incision pain and inflammatory stress response after orthopedic surgery.展开更多
Objective:To study the effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery.Methods: Patients undergoing abdominal surgery in our hospi...Objective:To study the effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery.Methods: Patients undergoing abdominal surgery in our hospital between May 2015 and March 2017 were selected and randomly divided into two groups, intervention group received flurbiprofen axetil pretreatment combined with routine intravenous anesthesia, and the control group only accepted conventional intravenous anesthesia. The levels of pain neurotransmitters and cytokines, stress hormones and mediators in serum were detected before operation as well as 12 h and 24 h after operation.Results: 12 h and 24 h after operation, serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of both groups of patients were significantly higher than those before operation while SOD, GHS-Px and HO-1 levels were significantly lower than those before operation, and serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of intervention group 12 h and 24 h after operation were significantly lower than those of control group while SOD, GHS-Px and HO-1 levels were significantly higher than those of control group.Conclusion:Flurbiprofen axetil pretreatment can reduce the pain degree and stress response after abdominal surgery.展开更多
Background Systemic non-steroidal anti-inflammatory drugs have been evaluated for their possible preemptive analgesic effects.The efficacy of flurbiprofen axetil for preemptive analgesia in patients undergoing radical...Background Systemic non-steroidal anti-inflammatory drugs have been evaluated for their possible preemptive analgesic effects.The efficacy of flurbiprofen axetil for preemptive analgesia in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach needs further investigation.The aim of this study was to research the preemptive analgesic effects of flurbiprofen axetil in thoracic surgery,and the influence of preoperative administration on postoperative respiratory function.Methods This randomized,double-blind,controlled trial enrolled 60 patients undergoing radical resection of esophageal carcinoma via the left thoracic approach.Anesthesia management was standardized.Each patient was randomly assigned to receive either 100 mg flurbiprofen axetil intravenously 15 minutes before incision （PA group） or intravenous normal saline as a control （C group）.Postoperative analgesia was with sufentanil delivered by patient-controlled analgesia pump.Postoperative sufentanil consumption,visual analog scale pain scores,plasma levels of interleukin-8,and oxygenation index were measured.Results Compared with the preoperative baseline,postoperative patients in the PA group had no obvious increase in pain scores （P 〉0.05）,but patients in the C group had significantly increased pain scores （P〈0.05）.Pain scores in the C group were significantly higher at 24 hours postoperatively than preoperatively.Intergroup comparisons showed lower visual analog scale scores at 2-24 hours postoperatively in the PA group than the C group （P 〈0.05）.Sufentanil consumption and plasma interleukin-8 levels at 2 and 12 hours postoperatively were significantly lower in the PA group than the C group （P 〈0.05）.The oxygenation index at 2 and 12 hours postoperatively was significantly higher in the PA group than the C group （P〈0.05）.Conclusions Intravenous flurbiprofen axetil appears to have a preemptive analgesic effect in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach,and appears to contribute to recovery of respiratorv function and to reduction of the postoperative inflammatory reaction.展开更多
It is known that opioids produce postoperative analgesia, while it can also cause, especially in large doses, side effects like nausea, vomiting, constipation, syncope, skin itching, urinary retention and even respira...It is known that opioids produce postoperative analgesia, while it can also cause, especially in large doses, side effects like nausea, vomiting, constipation, syncope, skin itching, urinary retention and even respiratory inhibition. These factors have all greatly limited its clinical use for treating postoperative pain. Meanwhile, non-steroidal anti-inflammatory drugs （NSAIDs） play an increasingly important role in postoperative analgesia. Some studies suggest that NSAIDS may be neural protective in cerebral ischemic conditions.展开更多
Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. Thi...Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.展开更多
Background Our previous papers indicate that flurbiprofen axetil （FA）, a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could ...Background Our previous papers indicate that flurbiprofen axetil （FA）, a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y （PPAR-y） after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley （SD） rats were randomly assigned into six groups （n=8 in each group）： animals in group ischemia/reperfusion （I/R） only received 120-minute transient middle cerebral artery occlusion （tMCAO）; animals in group I/R ＋FA were administered FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋FA＋GW9662 were administered GW9662 （a PPAR-Y inhibitor, 1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset and FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋GW9662 were administered GW9662 （1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R ＋DMSO were administered 3% DMSO （vehicle of GW9662, 1 ml/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score （NDS） were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） 10 g/L staining. Results NDS was significantly increased in group I/R＋FA （12.0 （10.0-15.0））, group I/R＋FA＋GW9662 （10.0 （8.0-12.0））, and in group I/R＋FA＋DMSO （12.0 （9.0-14.0）） at 72 hours after reperfusion compared with those in group I/R （7.5 （6.0-10.0））. NDS was conspicuously different between group I/R＋FA （12.0 （10.0-15.0）） and group I/R＋FA＋GW9662 （10.0 （8.0-12.0））. MBIVP in group I/R （（45.82±8.83）%） was significantly greater than that in group I/R＋FA （（23.52±9.90）%）, group I/R＋FA＋GW9662 （（33.17±7.15）%）; MBIVP in group I/R＋FA （（23.52±9.90）%） was significantly smaller than that in group I/R＋FA＋GW9662 （（33.17±7.15）%）. Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.展开更多
Cefuroxime axetil,a second-generation cephalosporin antibiotic,has long been utilized to treat various bacterial infections.However,recent advances in nanotechnology have provided new directions for enhancing its effe...Cefuroxime axetil,a second-generation cephalosporin antibiotic,has long been utilized to treat various bacterial infections.However,recent advances in nanotechnology have provided new directions for enhancing its effectiveness through the development of innovative nanoformulations.Cefuroxime axetil,which is classified as aβ-lactam agent,has a broad spectrum of activity against both gram-positive and gram-negative microorganisms.This drug exists in polymorphous crystalline and amorphous forms,the latter of which exhibits superior bioavailability.This review explores the pharmacokinetic and various pharmacodynamic properties and mechanisms of action of cefuroxime axetil.Moreover,the challenges posed by the drug’s poor aqueous solubility and bioavailability,and the potential of nanoformulations to address these limitations and enhance the therapeutic efficacy of this agent,are discussed.展开更多
Objective:To investigate the effect of preemptive analgesia withflurbiprofen axetil injection on the analgesic effect,inflammatory response,stress response and immune response in patients undergoing thoracoscopic lobe...Objective:To investigate the effect of preemptive analgesia withflurbiprofen axetil injection on the analgesic effect,inflammatory response,stress response and immune response in patients undergoing thoracoscopic lobectomy.Methods:92 patients with early non-small cell lung cancer who underwent thoracoscopic lobectomy from January 2016 to March 2018 in our hospital were divided into observation group and control group according to the method of random digital table,46 cases in each group.The control group was given routine perioperative analgesia,the observation group was given advanced analgesia mode,and the visual simulation scoring method(visual)was used to observe the patients in the two groups at 4,12,24 and 48 h after operation The results showed that the level of inflammation factor,stress response factor and immune response were significantly higher than that of before operation(T0),when anesthesia woke up(T1),12 hours after operation(T2),24 h after operation(T3)and 48 h after operation(T4).Results:(1)The VAS score of the observation group was significantly lower than that of the control group(P<0.05)at 4,12,24 and 48 h after operation;(2)The levels of IL-6,IL-10,SP-A and TNF-αin the two groups were significantly lower than that of the control group(P<0.05)The level of factor-α,TNF-α)was higher than that of to time point,and showed an upward trend;the level of IL-6,IL-10,TNF-α,SP-A decreased gradually at T3,T4 time points,the level of IL-6,TNF-α,SP-A in T1,T2,T3,T4 time points in the observation group was lower than that of the control group,and the level of IL-10 was higher than that of the control group(P<0.05);(3)Compared with T0 time point,the epinephrine(EPIPH)at T1,T2,T3,T4 time points in the two groups The levels of rine,e,noradrenaline,NE and cortisol in the observation group increased first and then decreased;the levels of E,NE and cor in the observation group were lower than those in the control group at T1,T2,T3 and T4 time points(P<0.05);and(4)Compared with T0 time point,the serum IgG,IgM and IgA levels in the two groups decreased gradually at T1,T2,T3 and T4 time points,but the observation group The levels of IgG,IgM and IgA in serum of group A were higher than those of group B(P<0.05).Conclusion:Preemptive analgesia with flurbiprofen axetil injection can significantly improve the postoperative pain,reduce the level of ;inflammation,reduce the stress response and increase the level of immune response.展开更多
文摘The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil(CFA), were prepared with β-cyclodextrin(βCD) with or without addition of L-arginine(ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency(CE) of βCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL(linear) type of solubility curve in presence and absence of ARG, the CE and association constant(Ks) of βCD towards CFA were significantly promoted in presence of ARG,justifying its use as a ternary component. The solid systems of CFA with βCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning calorimetry(DSC), X-ray powder diffractometry(XRPD), scanning electron microscopy(SEM), and saturation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA inside βCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation with βCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclusion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA via βCD complexation.
基金the National Nature Science Foundation of China(No.81173008)from Project for Excellent Talents of Liaoning Province(No.LR20110028)from Program for New Century Excellent Talents in University(No.NCET-12-1015).
文摘Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared by means of wet granulation method and solid dispersion method.Binders,suspending agents and other compositions involved in the formulation were optimized.The differential scanning calorimetry(DSC)analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier,which contributed to an improvement of the dissolution rate.Taste evaluation was performed by three volunteers and taste masking was successfully achieved by the methods mentioned above.A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations,i.e.,two self-made dry suspensions and the commercial one.With a better release characteristic and a satisfying taste masking ability,the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs.The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension,respectively.The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability.
文摘The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR spectroscopy to study the possible drug-drug or drug-excipient (s) interaction in case of concomitant oral administration of paracetamol with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime axetil and their commercially available suspensions, Amoxil?, Azithromax? and Zinnat? were used. DSC curves for paracetamol, pure antibiotics, commercially available antibiotics and all binary mixtures used in this study showed drug-drug or drug-excipient (s) physical interaction and indicated a possible chemical interaction. To confirm chemical drug-drug or drug-excipient (s) interaction additional ATR-IR spectra for all samples used in this study were obtained. Results obtained from ATR-IR spectra showed drug-excipient (s) interaction in Zinnat?, Azithromax? and binary mixture Azithromax?-paracetamol, while chemical drug-drug interaction was not observed. From this study it can be concluded that the concomitant oral administration of paracetamol with commercially available antibiotics used in this study is not recommended and duration of two hours between the oral administrations of these drugs is strongly recommended to avoid drug-drug or drug-excipient (s) interaction.
文摘Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.
文摘This investigation was undertaken to enhance the solubility and consequent antibacterial activity of cefuroxime axetil (CA), a </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-lactamase-stable broad spectrum second generation cephalosporin through solid dispersion (SD) technique. For this purpose, CA loaded SDs (CSDs) were prepared by solvent evaporation method using different concentrations of microcrystalline cellulose (MCC) as carrier. The CSDs were characterized by </span><i><span style="font-family:Verdana;">in-vitro</span></i><span style="font-family:Verdana;"> dissolution study, thermal analysis (DSC), crystallinity (PXRD), interactions (FTIR) and morphology (SEM). Among the formulations, CSD-2 showed the highest dissolution rate which was 2.59-fold higher than pure CA with a drug-carrier (CA: MCC) ratio of 1:3. Enhanced dissolution rate was attributed to conversion of drug from crystalline to amorphous state during preparation of SDs, which was validated by DSC, PXRD, FTIR and SEM analyses. Antibacterial activity of CSD-2 against </span><i><span style="font-family:Verdana;">Staphylococcus aureus</span></i><span style="font-family:Verdana;"> (ATCC 25923) and </span><i><span style="font-family:Verdana;">Escherichia coli</span></i><span style="font-family:Verdana;"> (ATCC 25922) showed 1.94- and 6.75-fold higher relative zone of inhibition (RZOI), respectively than pure CA. CSD-2 has been found to be the most effective optimized formulation in terms of both enhanced dissolution rate and antibacterial activity. Thus, it can be an effective alternative to conventional dosage forms of CA. However, further investigations are needed to validate its pharmacokinetic properties, </span><i><span style="font-family:Verdana;">in-vivo </span></i><span style="font-family:Verdana;">antibacterial efficacy and safety before recommending as a novel
文摘Objective: To investigate the effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity. Methods: Patients who underwent knee replacement in People's Hospital of Dongxihu District between April 2015 and January 2018 were selected as the research subjects and randomly divided into the experimental group who accepted flurbiprofen axetil combined with patient-controlled intravenous analgesia and the control group who accepted patient-controlled intravenous analgesia alone. The contents of cytokines and HPA axis-related hormones in serum were measured before surgery as well as 1 d and 3 d after surgery;the contents of cytokines in joint fluid were measured 1 d and 3 d after surgery. Results: Compared with those of same group before surgery, NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels of both groups were increasing 1 d and 3 d after surgery, and NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels in serum as well as PGE2, OPN, TGF-β1, FGF21, CXCL12 and YKL-40 in joint fluid of experimental group 1 d and 3 d after surgery were lower than those of control group. Conclusion: Flurbiprofen axetil analgesia after knee replacement can reduce the release of cytokines in serum and joint fluid, and inhibit the activity of HPA axis, and its analgesic effect is exact.
文摘Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underwent operative treatment of femoral neck fracture in Guangyuan Hospital of Traditional Chinese Medicine between March 2014 and December 2017 were selected as the research subjects. All patients were randomly divided into the experimental group who accepted flurbiprofen axetil intervention before induction + routine anesthesia induction and maintenance, and the control group who accepted routine anesthesia induction and maintenance, and each group included 43 cases. The pain levels of the two groups were assessed 24 h after surgery;the levels of pain mediators and inflammatory stress molecules in serum as well as the expression intensity of inflammatory stress molecules in peripheral blood were determined before surgery and 24 h after surgery.Results:24 h after surgery, serum SP, NPY, PGE2, TNF-α, IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of both groups were significantly higher than those before surgery, and NRS pain score, serum SP, NPY, PGE2, TNF- , IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of experimental group 24 h after surgery were significantly lower than those of control group.Conclusions:Flurbiprofen axetil intervention before induction can improve and inhibit the incision pain and inflammatory stress response after orthopedic surgery.
文摘Objective:To study the effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery.Methods: Patients undergoing abdominal surgery in our hospital between May 2015 and March 2017 were selected and randomly divided into two groups, intervention group received flurbiprofen axetil pretreatment combined with routine intravenous anesthesia, and the control group only accepted conventional intravenous anesthesia. The levels of pain neurotransmitters and cytokines, stress hormones and mediators in serum were detected before operation as well as 12 h and 24 h after operation.Results: 12 h and 24 h after operation, serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of both groups of patients were significantly higher than those before operation while SOD, GHS-Px and HO-1 levels were significantly lower than those before operation, and serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of intervention group 12 h and 24 h after operation were significantly lower than those of control group while SOD, GHS-Px and HO-1 levels were significantly higher than those of control group.Conclusion:Flurbiprofen axetil pretreatment can reduce the pain degree and stress response after abdominal surgery.
基金This study was supported by the National Natural Science Foundation of China （No.30872433）.
文摘Background Systemic non-steroidal anti-inflammatory drugs have been evaluated for their possible preemptive analgesic effects.The efficacy of flurbiprofen axetil for preemptive analgesia in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach needs further investigation.The aim of this study was to research the preemptive analgesic effects of flurbiprofen axetil in thoracic surgery,and the influence of preoperative administration on postoperative respiratory function.Methods This randomized,double-blind,controlled trial enrolled 60 patients undergoing radical resection of esophageal carcinoma via the left thoracic approach.Anesthesia management was standardized.Each patient was randomly assigned to receive either 100 mg flurbiprofen axetil intravenously 15 minutes before incision （PA group） or intravenous normal saline as a control （C group）.Postoperative analgesia was with sufentanil delivered by patient-controlled analgesia pump.Postoperative sufentanil consumption,visual analog scale pain scores,plasma levels of interleukin-8,and oxygenation index were measured.Results Compared with the preoperative baseline,postoperative patients in the PA group had no obvious increase in pain scores （P 〉0.05）,but patients in the C group had significantly increased pain scores （P〈0.05）.Pain scores in the C group were significantly higher at 24 hours postoperatively than preoperatively.Intergroup comparisons showed lower visual analog scale scores at 2-24 hours postoperatively in the PA group than the C group （P 〈0.05）.Sufentanil consumption and plasma interleukin-8 levels at 2 and 12 hours postoperatively were significantly lower in the PA group than the C group （P 〈0.05）.The oxygenation index at 2 and 12 hours postoperatively was significantly higher in the PA group than the C group （P〈0.05）.Conclusions Intravenous flurbiprofen axetil appears to have a preemptive analgesic effect in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach,and appears to contribute to recovery of respiratorv function and to reduction of the postoperative inflammatory reaction.
文摘It is known that opioids produce postoperative analgesia, while it can also cause, especially in large doses, side effects like nausea, vomiting, constipation, syncope, skin itching, urinary retention and even respiratory inhibition. These factors have all greatly limited its clinical use for treating postoperative pain. Meanwhile, non-steroidal anti-inflammatory drugs （NSAIDs） play an increasingly important role in postoperative analgesia. Some studies suggest that NSAIDS may be neural protective in cerebral ischemic conditions.
基金This study was supported by a grant from the National Nature Science Foundation of China （No. 30872445）.
文摘Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30872445）.
文摘Background Our previous papers indicate that flurbiprofen axetil （FA）, a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y （PPAR-y） after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley （SD） rats were randomly assigned into six groups （n=8 in each group）： animals in group ischemia/reperfusion （I/R） only received 120-minute transient middle cerebral artery occlusion （tMCAO）; animals in group I/R ＋FA were administered FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋FA＋GW9662 were administered GW9662 （a PPAR-Y inhibitor, 1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset and FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋GW9662 were administered GW9662 （1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R ＋DMSO were administered 3% DMSO （vehicle of GW9662, 1 ml/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score （NDS） were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） 10 g/L staining. Results NDS was significantly increased in group I/R＋FA （12.0 （10.0-15.0））, group I/R＋FA＋GW9662 （10.0 （8.0-12.0））, and in group I/R＋FA＋DMSO （12.0 （9.0-14.0）） at 72 hours after reperfusion compared with those in group I/R （7.5 （6.0-10.0））. NDS was conspicuously different between group I/R＋FA （12.0 （10.0-15.0）） and group I/R＋FA＋GW9662 （10.0 （8.0-12.0））. MBIVP in group I/R （（45.82±8.83）%） was significantly greater than that in group I/R＋FA （（23.52±9.90）%）, group I/R＋FA＋GW9662 （（33.17±7.15）%）; MBIVP in group I/R＋FA （（23.52±9.90）%） was significantly smaller than that in group I/R＋FA＋GW9662 （（33.17±7.15）%）. Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.
文摘Cefuroxime axetil,a second-generation cephalosporin antibiotic,has long been utilized to treat various bacterial infections.However,recent advances in nanotechnology have provided new directions for enhancing its effectiveness through the development of innovative nanoformulations.Cefuroxime axetil,which is classified as aβ-lactam agent,has a broad spectrum of activity against both gram-positive and gram-negative microorganisms.This drug exists in polymorphous crystalline and amorphous forms,the latter of which exhibits superior bioavailability.This review explores the pharmacokinetic and various pharmacodynamic properties and mechanisms of action of cefuroxime axetil.Moreover,the challenges posed by the drug’s poor aqueous solubility and bioavailability,and the potential of nanoformulations to address these limitations and enhance the therapeutic efficacy of this agent,are discussed.
文摘Objective:To investigate the effect of preemptive analgesia withflurbiprofen axetil injection on the analgesic effect,inflammatory response,stress response and immune response in patients undergoing thoracoscopic lobectomy.Methods:92 patients with early non-small cell lung cancer who underwent thoracoscopic lobectomy from January 2016 to March 2018 in our hospital were divided into observation group and control group according to the method of random digital table,46 cases in each group.The control group was given routine perioperative analgesia,the observation group was given advanced analgesia mode,and the visual simulation scoring method(visual)was used to observe the patients in the two groups at 4,12,24 and 48 h after operation The results showed that the level of inflammation factor,stress response factor and immune response were significantly higher than that of before operation(T0),when anesthesia woke up(T1),12 hours after operation(T2),24 h after operation(T3)and 48 h after operation(T4).Results:(1)The VAS score of the observation group was significantly lower than that of the control group(P<0.05)at 4,12,24 and 48 h after operation;(2)The levels of IL-6,IL-10,SP-A and TNF-αin the two groups were significantly lower than that of the control group(P<0.05)The level of factor-α,TNF-α)was higher than that of to time point,and showed an upward trend;the level of IL-6,IL-10,TNF-α,SP-A decreased gradually at T3,T4 time points,the level of IL-6,TNF-α,SP-A in T1,T2,T3,T4 time points in the observation group was lower than that of the control group,and the level of IL-10 was higher than that of the control group(P<0.05);(3)Compared with T0 time point,the epinephrine(EPIPH)at T1,T2,T3,T4 time points in the two groups The levels of rine,e,noradrenaline,NE and cortisol in the observation group increased first and then decreased;the levels of E,NE and cor in the observation group were lower than those in the control group at T1,T2,T3 and T4 time points(P<0.05);and(4)Compared with T0 time point,the serum IgG,IgM and IgA levels in the two groups decreased gradually at T1,T2,T3 and T4 time points,but the observation group The levels of IgG,IgM and IgA in serum of group A were higher than those of group B(P<0.05).Conclusion:Preemptive analgesia with flurbiprofen axetil injection can significantly improve the postoperative pain,reduce the level of ;inflammation,reduce the stress response and increase the level of immune response.
