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
Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available form...Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.展开更多
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
Flurbiprofen 1, an excellent nonsteroidal antiinflammatory drug, was synthesized in 5 steps in 69% overall yield. The key step of constructing the biaryl fragment was successfully achieved via Pd/C-catalyzed Suzuki co...Flurbiprofen 1, an excellent nonsteroidal antiinflammatory drug, was synthesized in 5 steps in 69% overall yield. The key step of constructing the biaryl fragment was successfully achieved via Pd/C-catalyzed Suzuki coupling reaction in water using sodium tetraphenylborate as phenylation reagent.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
Flurbiprofen, a non-steroidal anti-inflammatory agent, is used to treat rheumatoid arthritis and sore throat (1)However, it gave poor water solubility, and various solubilization technique such as self-microemulsifyin...Flurbiprofen, a non-steroidal anti-inflammatory agent, is used to treat rheumatoid arthritis and sore throat (1)However, it gave poor water solubility, and various solubilization technique such as self-microemulsifying drug delivery system(SMEDDS) has been used to improve the solubility, dissolution and oral bioavailability [2].The objective of this work was to develop redispersible solidified SMEDDS containing water-insoluble flurbiprofen with enhanced solubility.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
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
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
The partitioning of two non-steroidal anti-inflammatory drugs (NSAIDs), flurbiprofen and ketoprofen, into cationic cetyltrimethylammonium micelles was investigated using semi-equilibrium dialysis at 37℃ in phosphate ...The partitioning of two non-steroidal anti-inflammatory drugs (NSAIDs), flurbiprofen and ketoprofen, into cationic cetyltrimethylammonium micelles was investigated using semi-equilibrium dialysis at 37℃ in phosphate buffered saline. The micellar-water solubilization equilibrium constants for both NSAIDs, in their deprotonated forms, were observed to decrease linearly with increasing mole fraction of drug in micelles. For flurbiprofen, the solubilization constant in the limit as mole fraction of drug in micelles approaches zero was found to be 11,200 (co = 1 M), while for ketoprofen the value was 1950 (co = 1 M). Using 1H-NMR and UV spectroscopic techniques, the locus of solubilization for ketoprofen was found to be towards the charged exterior of the micelles, in the Stern layer, whereas flurbiprofen was found to solubilize more in the micellar interior.展开更多
We developed a novel topical non-steroidal anti-inflammatory drug (NSAID)patch, S(+)-flurbiprofen plaster, (SFPP), containing S(+)-flurbiprofen (SFP), an enantiomer of flurbiprofen (FP). In a previous study conducted ...We developed a novel topical non-steroidal anti-inflammatory drug (NSAID)patch, S(+)-flurbiprofen plaster, (SFPP), containing S(+)-flurbiprofen (SFP), an enantiomer of flurbiprofen (FP). In a previous study conducted in an animal model, we showed good skin absorption and potent analgesic efficacy of SFPP. In this study, to examine the superior features, as an NSAID patch, of SFP as compared to FP and R(-)-flurbiprofen (RFP), we tested the stereospecificity of SFP actions on Prostaglandin E2 (PGE2) inhibition in rat inflammatory leukocytes and in the binding activity of the drug to cells, and also the in vitro skin permeability of the drug in the Yucatan micropig (YMP). SFP showed potent inhibitory activity on PGE2 production from peritoneal leukocytes stimulated with a bacterial suspension, as compared to RFP and FP. The half maximal (50%) inhibitory concentration (IC50) values were 14 nM for SFP, 52 nM for FP, and 17,000 nM for RFP. In the cell binding study, significant and rapid increase of SFP binding to polymorphonuclear leucocytes (PMNs) was observed at 5 min after incubation, eventually reaching a steady state. SFP showed significantly higher binding activity for the inflammatory leucocytes as compared to RFP, suggesting its superior transfer potency. The skin permeability profile of SFP, RFP and FP in the YMP model showed that the rank order of the cumulative amount of permeated compounds in the skin was SFP > RFP > FP. The steady-state permeation rate (Flux) of SFP was significantly higher than that of FP (4.89 and 1.55 mg/cm2/h, respectively, p = 0.0068), indicating the remarkably superior skin permeability of SFP. SFP exerted potent inhibitory activity on PGE2 production and superior binding activity to the PMNs and skin permeability, as compared to FP and RFP. These results suggest that SFP possesses favorable characteristics for use as an active ingredient in the NSAID patch.展开更多
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financially supported by the National Postdoctoral Foundation of China(No.2023M730375)Liaoning Province Department of Education Project(No.LJKMZ20221365)the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215)。
文摘Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.
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We are grateful to Liaoning Natural Science Foundation for the Talent Doctors Fund(No.20041037)Magnus Ehrnrooths Foundation of Finland for the financial supports.
文摘Flurbiprofen 1, an excellent nonsteroidal antiinflammatory drug, was synthesized in 5 steps in 69% overall yield. The key step of constructing the biaryl fragment was successfully achieved via Pd/C-catalyzed Suzuki coupling reaction in water using sodium tetraphenylborate as phenylation reagent.
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Flurbiprofen, a non-steroidal anti-inflammatory agent, is used to treat rheumatoid arthritis and sore throat (1)However, it gave poor water solubility, and various solubilization technique such as self-microemulsifying drug delivery system(SMEDDS) has been used to improve the solubility, dissolution and oral bioavailability [2].The objective of this work was to develop redispersible solidified SMEDDS containing water-insoluble flurbiprofen with enhanced solubility.
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The partitioning of two non-steroidal anti-inflammatory drugs (NSAIDs), flurbiprofen and ketoprofen, into cationic cetyltrimethylammonium micelles was investigated using semi-equilibrium dialysis at 37℃ in phosphate buffered saline. The micellar-water solubilization equilibrium constants for both NSAIDs, in their deprotonated forms, were observed to decrease linearly with increasing mole fraction of drug in micelles. For flurbiprofen, the solubilization constant in the limit as mole fraction of drug in micelles approaches zero was found to be 11,200 (co = 1 M), while for ketoprofen the value was 1950 (co = 1 M). Using 1H-NMR and UV spectroscopic techniques, the locus of solubilization for ketoprofen was found to be towards the charged exterior of the micelles, in the Stern layer, whereas flurbiprofen was found to solubilize more in the micellar interior.
文摘We developed a novel topical non-steroidal anti-inflammatory drug (NSAID)patch, S(+)-flurbiprofen plaster, (SFPP), containing S(+)-flurbiprofen (SFP), an enantiomer of flurbiprofen (FP). In a previous study conducted in an animal model, we showed good skin absorption and potent analgesic efficacy of SFPP. In this study, to examine the superior features, as an NSAID patch, of SFP as compared to FP and R(-)-flurbiprofen (RFP), we tested the stereospecificity of SFP actions on Prostaglandin E2 (PGE2) inhibition in rat inflammatory leukocytes and in the binding activity of the drug to cells, and also the in vitro skin permeability of the drug in the Yucatan micropig (YMP). SFP showed potent inhibitory activity on PGE2 production from peritoneal leukocytes stimulated with a bacterial suspension, as compared to RFP and FP. The half maximal (50%) inhibitory concentration (IC50) values were 14 nM for SFP, 52 nM for FP, and 17,000 nM for RFP. In the cell binding study, significant and rapid increase of SFP binding to polymorphonuclear leucocytes (PMNs) was observed at 5 min after incubation, eventually reaching a steady state. SFP showed significantly higher binding activity for the inflammatory leucocytes as compared to RFP, suggesting its superior transfer potency. The skin permeability profile of SFP, RFP and FP in the YMP model showed that the rank order of the cumulative amount of permeated compounds in the skin was SFP > RFP > FP. The steady-state permeation rate (Flux) of SFP was significantly higher than that of FP (4.89 and 1.55 mg/cm2/h, respectively, p = 0.0068), indicating the remarkably superior skin permeability of SFP. SFP exerted potent inhibitory activity on PGE2 production and superior binding activity to the PMNs and skin permeability, as compared to FP and RFP. These results suggest that SFP possesses favorable characteristics for use as an active ingredient in the NSAID patch.