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Zeitschriftendaten
Format
Zeitschrift
eISSN
1846-9558
ISSN
1330-0075
Erstveröffentlichung
28 Feb 2007
Erscheinungsweise
4 Hefte pro Jahr
Sprachen
Englisch

Suche

Volumen 64 (2014): Heft 1 (March 2014)

Zeitschriftendaten
Format
Zeitschrift
eISSN
1846-9558
ISSN
1330-0075
Erstveröffentlichung
28 Feb 2007
Erscheinungsweise
4 Hefte pro Jahr
Sprachen
Englisch

Suche

10 Artikel
Uneingeschränkter Zugang

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 1 - 13

Zusammenfassung

Abstract

Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.

Schlüsselwörter

  • entacapone
  • in-line crystallization monitoring
  • multivariate analysis
  • polymorphism
  • Raman spectroscopy
  • SWAXS
Uneingeschränkter Zugang

Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in pharmaceutical formulations: Application of quinone-based fluorophores and enhanced native fluorescence

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 15 - 28

Zusammenfassung

Abstract

Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM) and linezolid (LIN) in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A) and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B) as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5) at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.

Schlüsselwörter

  • gemifloxacin mesylate
  • linezolid
  • 7,7,8,8-tetracyanoquinodimethane
  • 2,5-dichloro-3,6-dihydroxy-p-ben- -zoquinone
  • fluorimetry
  • charge transfer complex
Uneingeschränkter Zugang

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 29 - 44

Zusammenfassung

Abstract

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels

Schlüsselwörter

  • dextromethorphan
  • solid dispersion
  • in situ gelling
  • alginate gels
Uneingeschränkter Zugang

Comparative bioavailability of two oral formulations of clopidogrel: Determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 45 - 62

Zusammenfassung

Abstract

Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka’s formulation to the innovator’s formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations.

Schlüsselwörter

  • bioavailability
  • food effect
  • clopidogrel
  • clopidogrel carboxylic acid
Uneingeschränkter Zugang

High throughput microwell spectrophotometric assay for olmesartan medoxomil in tablets based on its charge-transfer reaction with DDQ

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 63 - 75

Zusammenfassung

Abstract

The study describes the development and validation of a new microwell-based spectrophotometric assay for determination of olmesartan medoxomil (OLM) in tablets. The formation of a colored charge-transfer (CT) complex between OLM as an n-electron donor and 2,3-dichloro- -5,6-dicyano-1,4-benzoquinone (DDQ) as a p-electron acceptor was investigated, and employed as the basis for the development of the new assay. The proposed assay was conducted in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm with a microplate reader. Optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, a linear relationship with a good correlation coefficient was found between the absorbance and the concentration of OLM in the range of 2-200 μg per well. The limits of detection and quantitation were 0.53 and 1.61 μg per well, respectively. No interference was observed from the excipients present in OLM tablets or from hydrochlorothiazide and amlodipine besylate that were co-formulated with OLM in some of its formulations. The assay was successfully applied to the analysis of OLM in tablets with good accuracy and precision. The assay described herein has a great practical value in the routine analysis of OLM in quality control laboratories, since it has a high throughput property and consumes low volumes of organic solvent. It thus offers a reduction in the exposure of analysts to the toxic effects of organic solvents, as well as a reduction in the cost of analysis.

Schlüsselwörter

  • olmesartan medoxomil
  • spectrophotometry
  • charge-transfer complex
  • 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
  • microwell assay
Uneingeschränkter Zugang

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 77 - 88

Zusammenfassung

Abstract

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.

Schlüsselwörter

  • ciprofloxacin
  • dissolution
  • drug interactions
  • solubility
  • solid state characterisation
Uneingeschränkter Zugang

Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 89 - 104

Zusammenfassung

Abstract

Eudragit E (EE)-sodium alginate (SA) polyelectrolyte complexes (PECs) were prepared at pH 4 and 5.8 using sodium alginate of high (SAH) and low viscosity (SAL). The optimum EE-SA complexation mass ratio was determined using viscosity measurements. Interactions between EE and SA in PECs were characterized by Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Diltiazem hydrochloride (DTZ HCl) tablets were prepared using the prepared EE-SA PECs and their physical mixtures at different ratios as matrices. Tablets were evaluated for swelling characteristics and in vitro drug release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3) as matrices were effective in achieving sustained release of DTZ HCl, where the percent drug released was significantly (p < 0.05) decreased compared to that from tablets either containing the same ratios of EE-SAL physical mixtures or the preformed EE- -SAH and EE-SAL PECs.

Schlüsselwörter

  • polyelectrolyte complex
  • diltiazem hydrochloride
  • Eudragit E 100
  • sodium alginate
  • viscosity
  • tablet matrix
Uneingeschränkter Zugang

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 105 - 115

Zusammenfassung

Abstract

C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left ventricular short axis fractional shortening (LVFS), accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover, myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2) activity was decreased. The ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2) expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT1R) and protein kinase C (PKC)b2. The possible underlying mechanism might be the regulation of myocardial AT1R-PKCb2-Ca2+ handling proteins.

Schlüsselwörter

  • pitavastatin
  • dilated cardiomyopathy
  • calcium handling proteins
  • renin-angiotensin system
  • protein kinase Cβ2
Uneingeschränkter Zugang

GSTP1, GSTM1 and GSTT1 genetic polymorphisms and total serum GST concentration in stable male COPD

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 117 - 129

Zusammenfassung

Abstract

The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.

Schlüsselwörter

  • glutathione S-transferases (GST)
  • polymorphism
  • COPD
  • alpha-1-antitrypsin
  • lactate dehydrogenase
Uneingeschränkter Zugang

The effect of diclofenac on proliferation and production of growth factors by endothelial cells (HMEC-1) under hypoxia and inflammatory conditions

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 131 - 138

Zusammenfassung

Abstract

Diclofenac belongs to non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective COX inhibitors. The aim of this study was to examine the effect of diclofenac on endothelial cell proliferation under the influence of hypoxia or inflammatory conditions. Another goal was to check whether diclofenac modulates the secretion of angiogenic factors such as VEGF and bFGF in human microvascular endothelial cells (HMEC-1) in the presence of CoCl2 or lipopolysaccharide (LPS), which could influence the endothelial cells in an autocrine manner or other cells in a paracrine manner. HMEC-1 cells were treated with 0.1 and 0.3 mmol L-1 diclofenac in the presence of 100 μg mL-1 LPS or 200 μmol L-1 CoCl2. Diclofenac decreased cell viability under hypoxia and inflammatory conditions. The stimulation of bFGF secretion by LPS in microvascular endothelial cells (HMEC-1 cell) was attenuated by diclofenac. Diclofenac increased the secretion of VEGF induced by LPS and hypoxia.

Schlüsselwörter

  • LPS
  • VEGF
  • bFGF
  • diclofenac
  • hypoxia
  • endothelial cells
10 Artikel
Uneingeschränkter Zugang

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 1 - 13

Zusammenfassung

Abstract

Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.

Schlüsselwörter

  • entacapone
  • in-line crystallization monitoring
  • multivariate analysis
  • polymorphism
  • Raman spectroscopy
  • SWAXS
Uneingeschränkter Zugang

Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in pharmaceutical formulations: Application of quinone-based fluorophores and enhanced native fluorescence

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 15 - 28

Zusammenfassung

Abstract

Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM) and linezolid (LIN) in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A) and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B) as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5) at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.

Schlüsselwörter

  • gemifloxacin mesylate
  • linezolid
  • 7,7,8,8-tetracyanoquinodimethane
  • 2,5-dichloro-3,6-dihydroxy-p-ben- -zoquinone
  • fluorimetry
  • charge transfer complex
Uneingeschränkter Zugang

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 29 - 44

Zusammenfassung

Abstract

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels

Schlüsselwörter

  • dextromethorphan
  • solid dispersion
  • in situ gelling
  • alginate gels
Uneingeschränkter Zugang

Comparative bioavailability of two oral formulations of clopidogrel: Determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 45 - 62

Zusammenfassung

Abstract

Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka’s formulation to the innovator’s formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations.

Schlüsselwörter

  • bioavailability
  • food effect
  • clopidogrel
  • clopidogrel carboxylic acid
Uneingeschränkter Zugang

High throughput microwell spectrophotometric assay for olmesartan medoxomil in tablets based on its charge-transfer reaction with DDQ

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 63 - 75

Zusammenfassung

Abstract

The study describes the development and validation of a new microwell-based spectrophotometric assay for determination of olmesartan medoxomil (OLM) in tablets. The formation of a colored charge-transfer (CT) complex between OLM as an n-electron donor and 2,3-dichloro- -5,6-dicyano-1,4-benzoquinone (DDQ) as a p-electron acceptor was investigated, and employed as the basis for the development of the new assay. The proposed assay was conducted in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm with a microplate reader. Optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, a linear relationship with a good correlation coefficient was found between the absorbance and the concentration of OLM in the range of 2-200 μg per well. The limits of detection and quantitation were 0.53 and 1.61 μg per well, respectively. No interference was observed from the excipients present in OLM tablets or from hydrochlorothiazide and amlodipine besylate that were co-formulated with OLM in some of its formulations. The assay was successfully applied to the analysis of OLM in tablets with good accuracy and precision. The assay described herein has a great practical value in the routine analysis of OLM in quality control laboratories, since it has a high throughput property and consumes low volumes of organic solvent. It thus offers a reduction in the exposure of analysts to the toxic effects of organic solvents, as well as a reduction in the cost of analysis.

Schlüsselwörter

  • olmesartan medoxomil
  • spectrophotometry
  • charge-transfer complex
  • 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
  • microwell assay
Uneingeschränkter Zugang

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 77 - 88

Zusammenfassung

Abstract

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.

Schlüsselwörter

  • ciprofloxacin
  • dissolution
  • drug interactions
  • solubility
  • solid state characterisation
Uneingeschränkter Zugang

Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 89 - 104

Zusammenfassung

Abstract

Eudragit E (EE)-sodium alginate (SA) polyelectrolyte complexes (PECs) were prepared at pH 4 and 5.8 using sodium alginate of high (SAH) and low viscosity (SAL). The optimum EE-SA complexation mass ratio was determined using viscosity measurements. Interactions between EE and SA in PECs were characterized by Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Diltiazem hydrochloride (DTZ HCl) tablets were prepared using the prepared EE-SA PECs and their physical mixtures at different ratios as matrices. Tablets were evaluated for swelling characteristics and in vitro drug release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3) as matrices were effective in achieving sustained release of DTZ HCl, where the percent drug released was significantly (p < 0.05) decreased compared to that from tablets either containing the same ratios of EE-SAL physical mixtures or the preformed EE- -SAH and EE-SAL PECs.

Schlüsselwörter

  • polyelectrolyte complex
  • diltiazem hydrochloride
  • Eudragit E 100
  • sodium alginate
  • viscosity
  • tablet matrix
Uneingeschränkter Zugang

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 105 - 115

Zusammenfassung

Abstract

C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left ventricular short axis fractional shortening (LVFS), accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover, myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2) activity was decreased. The ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2) expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT1R) and protein kinase C (PKC)b2. The possible underlying mechanism might be the regulation of myocardial AT1R-PKCb2-Ca2+ handling proteins.

Schlüsselwörter

  • pitavastatin
  • dilated cardiomyopathy
  • calcium handling proteins
  • renin-angiotensin system
  • protein kinase Cβ2
Uneingeschränkter Zugang

GSTP1, GSTM1 and GSTT1 genetic polymorphisms and total serum GST concentration in stable male COPD

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 117 - 129

Zusammenfassung

Abstract

The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.

Schlüsselwörter

  • glutathione S-transferases (GST)
  • polymorphism
  • COPD
  • alpha-1-antitrypsin
  • lactate dehydrogenase
Uneingeschränkter Zugang

The effect of diclofenac on proliferation and production of growth factors by endothelial cells (HMEC-1) under hypoxia and inflammatory conditions

Online veröffentlicht: 25 Mar 2014
Seitenbereich: 131 - 138

Zusammenfassung

Abstract

Diclofenac belongs to non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective COX inhibitors. The aim of this study was to examine the effect of diclofenac on endothelial cell proliferation under the influence of hypoxia or inflammatory conditions. Another goal was to check whether diclofenac modulates the secretion of angiogenic factors such as VEGF and bFGF in human microvascular endothelial cells (HMEC-1) in the presence of CoCl2 or lipopolysaccharide (LPS), which could influence the endothelial cells in an autocrine manner or other cells in a paracrine manner. HMEC-1 cells were treated with 0.1 and 0.3 mmol L-1 diclofenac in the presence of 100 μg mL-1 LPS or 200 μmol L-1 CoCl2. Diclofenac decreased cell viability under hypoxia and inflammatory conditions. The stimulation of bFGF secretion by LPS in microvascular endothelial cells (HMEC-1 cell) was attenuated by diclofenac. Diclofenac increased the secretion of VEGF induced by LPS and hypoxia.

Schlüsselwörter

  • LPS
  • VEGF
  • bFGF
  • diclofenac
  • hypoxia
  • endothelial cells

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