Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcell...Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcellulose （EC） by the emulsion solvent diffusion technique. The release rate of mefformin from the microcapsules was highly dependent on the encapsulating formulation, thus being used as an index for formulation screening. Orthogonal experiments were performed to optimize the coating formulation. Results The final chosen formulation for coating of mefformin microcapsules were as follows： （ 1 ） the ratio of EC （20cps） to EC （45cps） was 50：50; （2） the ratio of plasticizer to coating materials was 20% ;and （3） the ratio of resin-mefformin complexes to coating materials was 5 ： 1. Conclusion The prolonged release microspheres of mefformin hydrochloride were successfully prepared.展开更多
Density（ρ）and viscosity（η）are measured for glycine,DL-α-alanine DL-α-valine,and DL-α-leucine in 0.05,0.10,0.15 and 0.20 mol·L^-1aqueous metformin hydrochloride at 308.15,313.15 and 318.15 K.The measured ...Density（ρ）and viscosity（η）are measured for glycine,DL-α-alanine DL-α-valine,and DL-α-leucine in 0.05,0.10,0.15 and 0.20 mol·L^-1aqueous metformin hydrochloride at 308.15,313.15 and 318.15 K.The measured values are used to estimate some important parameters,such as partial molal volume Vφ,standard partial molal volume Vφ^0,transfer volume ΔVφ^0,hydration number nH,the second derivative of infinite dilution of partial molal volume with respect to temperature,viz., ^2 Vφ^0 /T^2,viscosity B-coefficient,variation of B with temperature,viz., dB/dT,free energy of activation per mole of solvent Δμ1^＊0 and solute Δμ2^0＊ of the amino acids.These parameters are interpreted in terms of solute-solute and solute-solvent interactions and structure making/breaking ability of solutes in the given solution.In addition,Vφ^0,0 ΔVφ^0,viscosity B-coefficient,ΔB and Δμ2 ^0＊ are split into group contributions（NH3^＋ COO ^-）and -CH2 of the amino acids using their linear correlation and their behavior is discussed.展开更多
In order to teach students,the importance of conductometric titrations in this work,we present a laboratory experiment to quantify the amount of metformin hydrochloride in a tablet.The quantification was carried out t...In order to teach students,the importance of conductometric titrations in this work,we present a laboratory experiment to quantify the amount of metformin hydrochloride in a tablet.The quantification was carried out through the evaluation of the chloride by silver nitrate.The titration and the end point were followed by conductometric titration,as well as by potentiometric and visually by the Volhard method.In addition,the theoretical conductivities of the metformin hydrochloride solution were calculated when known volumes of titrant are added,using the limit conductivity data for each of the ions present in the literature.To simulate the conductometric titration,the calculated conductivity values were plotted based on the volume of silver nitrate added.A comparison between techniques is made in order to determine the best monitoring method,being this one conductimetry to detect the equivalence point for metformin hydrochloride with 0.99±0.03,according to relative standard deviation(%RSD).Simulated titration curves adequately describe obtained results in an experimental way.The conductometric titration is the best method for quantification since it shows less dispersion between obtained results and has the highest concordance among results.Their application is shown through the analysis and conductometric titration simulations.展开更多
Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent ye...Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.展开更多
A randomized, two-way, crossover study was conducted in 12 fasting, healthy, algerian volunteers to compare the bioavailability of two brands of metformin hydrochloride 850 mg coated tablets. The present study aimed t...A randomized, two-way, crossover study was conducted in 12 fasting, healthy, algerian volunteers to compare the bioavailability of two brands of metformin hydrochloride 850 mg coated tablets. The present study aimed to appreciate the bioequivalence of the generic product and to evaluate the intra-subject variability of this active substance in the Algerian population. The test brand was compared to Glucophage （Merck UK） as the reference product. The study was performed at the bioequivalence center of the national control laboratory for pharmaceuticals products from 03 to 04, 2011, in joint venture with specialized medical hospital center of E1 Hadi Flici, Algiers, Algeria. The drug was administered with 200 mL of water after a 10 h overnight fasting on two treatment days separated by one week washout period. After dosing, serial blood samples were collected for a period of 12 h. A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric （LC-MS/MS） method has been developed and validated for estimation of metformin in human plasma using propranolol as internal standard. The analytes were extracted from plasma by using the protein precipitation extraction technique. The assay was found to be linear over the range of 50-3000 ng/mL with a lower limit of quantitation of 50 ng/mL. Various pharmacokinetic parameters including AUC0-t, AUC0-∞, Cmax, Tmax, and T1/2 were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. The pharmacokinetical and statistical analysis was conducted with Kinetica 4.4.1. AUC0-t, AUC0-∞ and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval （[91.62 %, 115.66%] for AUC0-t, [92.07 %, 115.53 %] for AUC0-∞; [94.58%, 119.58 %] for Cmax） of test/reference ratio for these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Metformin hydrochloride test is bioequivalent to Glucophage.展开更多
Guar gum(GG)has drawn more interest from researchers in the last several decades for the controlled delivery of drugs.The aim of the research is to fabricate and evaluate an interpenetrating polymer network(IPN)based ...Guar gum(GG)has drawn more interest from researchers in the last several decades for the controlled delivery of drugs.The aim of the research is to fabricate and evaluate an interpenetrating polymer network(IPN)based nanocarriers system employing chemically modified GG to achieve controlled release of drug.In present study,we have reported the synthesis of carboxymethyl GG-chitosan IPN nanoparticles for controlled release of metformin hydrochloride.Carboxymethyl guar gum(CMGG)was synthesized and employed for developing IPN nanoparticles in combination with chitosan in varying polymeric ratios.A cross-linking agent,sodium tripolyphosphate(Na-TPP)was used for the synthesis of IPN colloidal suspension of nanoparticles which was lyophilized to obtain nanoparticles.The carboxymethylation of GG was confirmed through Fourier transform infra-red spectroscopy.The mean particle size was 440.6 nm indicating a polydispersity index of 0.528.The drug entrapment efficiency was found to vary between 67.461.64%to 88.232.02%.The differential scanning calorimetry study revealed the presence of amorphous metformin hydrochloride as a homogenous dispersion in nanoparticles(NPs)matrix.In vitro drug release study indicated controlled release ability of developed IPN matrix.A2 formulation(chitosan:CMGG-1:1)exhibited 78.110.27%release after 8 h.Antidiabetic evaluation performed in alloxan-treated diabetic rat model exhibited a prolonged hypoglycemic efficacy over 6 h,for A2 formulation treated group,compared to the group receiving only metformin HCl,which demonstrated a reduction in blood glucose levels for up to 4 h.The study findings demonstrated the efficacy of the CMGG-chitosan based IPN nanoparticulate system for sustained delivery of therapeutic agents.展开更多
文摘Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcellulose （EC） by the emulsion solvent diffusion technique. The release rate of mefformin from the microcapsules was highly dependent on the encapsulating formulation, thus being used as an index for formulation screening. Orthogonal experiments were performed to optimize the coating formulation. Results The final chosen formulation for coating of mefformin microcapsules were as follows： （ 1 ） the ratio of EC （20cps） to EC （45cps） was 50：50; （2） the ratio of plasticizer to coating materials was 20% ;and （3） the ratio of resin-mefformin complexes to coating materials was 5 ： 1. Conclusion The prolonged release microspheres of mefformin hydrochloride were successfully prepared.
文摘Density（ρ）and viscosity（η）are measured for glycine,DL-α-alanine DL-α-valine,and DL-α-leucine in 0.05,0.10,0.15 and 0.20 mol·L^-1aqueous metformin hydrochloride at 308.15,313.15 and 318.15 K.The measured values are used to estimate some important parameters,such as partial molal volume Vφ,standard partial molal volume Vφ^0,transfer volume ΔVφ^0,hydration number nH,the second derivative of infinite dilution of partial molal volume with respect to temperature,viz., ^2 Vφ^0 /T^2,viscosity B-coefficient,variation of B with temperature,viz., dB/dT,free energy of activation per mole of solvent Δμ1^＊0 and solute Δμ2^0＊ of the amino acids.These parameters are interpreted in terms of solute-solute and solute-solvent interactions and structure making/breaking ability of solutes in the given solution.In addition,Vφ^0,0 ΔVφ^0,viscosity B-coefficient,ΔB and Δμ2 ^0＊ are split into group contributions（NH3^＋ COO ^-）and -CH2 of the amino acids using their linear correlation and their behavior is discussed.
文摘In order to teach students,the importance of conductometric titrations in this work,we present a laboratory experiment to quantify the amount of metformin hydrochloride in a tablet.The quantification was carried out through the evaluation of the chloride by silver nitrate.The titration and the end point were followed by conductometric titration,as well as by potentiometric and visually by the Volhard method.In addition,the theoretical conductivities of the metformin hydrochloride solution were calculated when known volumes of titrant are added,using the limit conductivity data for each of the ions present in the literature.To simulate the conductometric titration,the calculated conductivity values were plotted based on the volume of silver nitrate added.A comparison between techniques is made in order to determine the best monitoring method,being this one conductimetry to detect the equivalence point for metformin hydrochloride with 0.99±0.03,according to relative standard deviation(%RSD).Simulated titration curves adequately describe obtained results in an experimental way.The conductometric titration is the best method for quantification since it shows less dispersion between obtained results and has the highest concordance among results.Their application is shown through the analysis and conductometric titration simulations.
基金funded by the National Natural Science Foundation of China(32102646)the Natural Science Foundation of Guangdong Province,China(2020A1515110315)+1 种基金the Start-up Research Project of Maoming Laboratory,China(2021TDQD002)the China Agriculture Research System of MOF and MARA(cars-35)。
文摘Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.
文摘A randomized, two-way, crossover study was conducted in 12 fasting, healthy, algerian volunteers to compare the bioavailability of two brands of metformin hydrochloride 850 mg coated tablets. The present study aimed to appreciate the bioequivalence of the generic product and to evaluate the intra-subject variability of this active substance in the Algerian population. The test brand was compared to Glucophage （Merck UK） as the reference product. The study was performed at the bioequivalence center of the national control laboratory for pharmaceuticals products from 03 to 04, 2011, in joint venture with specialized medical hospital center of E1 Hadi Flici, Algiers, Algeria. The drug was administered with 200 mL of water after a 10 h overnight fasting on two treatment days separated by one week washout period. After dosing, serial blood samples were collected for a period of 12 h. A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric （LC-MS/MS） method has been developed and validated for estimation of metformin in human plasma using propranolol as internal standard. The analytes were extracted from plasma by using the protein precipitation extraction technique. The assay was found to be linear over the range of 50-3000 ng/mL with a lower limit of quantitation of 50 ng/mL. Various pharmacokinetic parameters including AUC0-t, AUC0-∞, Cmax, Tmax, and T1/2 were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. The pharmacokinetical and statistical analysis was conducted with Kinetica 4.4.1. AUC0-t, AUC0-∞ and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval （[91.62 %, 115.66%] for AUC0-t, [92.07 %, 115.53 %] for AUC0-∞; [94.58%, 119.58 %] for Cmax） of test/reference ratio for these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Metformin hydrochloride test is bioequivalent to Glucophage.
文摘Guar gum(GG)has drawn more interest from researchers in the last several decades for the controlled delivery of drugs.The aim of the research is to fabricate and evaluate an interpenetrating polymer network(IPN)based nanocarriers system employing chemically modified GG to achieve controlled release of drug.In present study,we have reported the synthesis of carboxymethyl GG-chitosan IPN nanoparticles for controlled release of metformin hydrochloride.Carboxymethyl guar gum(CMGG)was synthesized and employed for developing IPN nanoparticles in combination with chitosan in varying polymeric ratios.A cross-linking agent,sodium tripolyphosphate(Na-TPP)was used for the synthesis of IPN colloidal suspension of nanoparticles which was lyophilized to obtain nanoparticles.The carboxymethylation of GG was confirmed through Fourier transform infra-red spectroscopy.The mean particle size was 440.6 nm indicating a polydispersity index of 0.528.The drug entrapment efficiency was found to vary between 67.461.64%to 88.232.02%.The differential scanning calorimetry study revealed the presence of amorphous metformin hydrochloride as a homogenous dispersion in nanoparticles(NPs)matrix.In vitro drug release study indicated controlled release ability of developed IPN matrix.A2 formulation(chitosan:CMGG-1:1)exhibited 78.110.27%release after 8 h.Antidiabetic evaluation performed in alloxan-treated diabetic rat model exhibited a prolonged hypoglycemic efficacy over 6 h,for A2 formulation treated group,compared to the group receiving only metformin HCl,which demonstrated a reduction in blood glucose levels for up to 4 h.The study findings demonstrated the efficacy of the CMGG-chitosan based IPN nanoparticulate system for sustained delivery of therapeutic agents.
