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Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

Buscar

Volumen 66 (2016): Edición 1 (March 2016)

Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

Buscar

12 Artículos
Acceso abierto

The therapeutic agents that target ATP-sensitive potassium channels

Publicado en línea: 07 Mar 2016
Páginas: 23 - 34

Resumen

Abstract

ATP-sensitive potassium (KATP) channels are a major drug target for the treatment of type-2 diabetes. KATP channels are ubiquitously expressed and link the metabolic state to electrical excitability. In pancreatic β-cells, KATP channels are crucial in the regulation of glucose-induced insulin secretion. Also, KATP channels are involved in the protection against neuronal seizures and ischaemic stress in the heart, brain and in the regulation of vascular smooth muscle tone. Functional KATP channels are hetero-octamers composed of two subunits, a pore forming Kir6, which is a member of the inwardly rectifying potassium channels family, and a regulatory sulphonylurea receptor (SUR). In response to nucleotides and pharmaceutical agonists and antagonists, SUR allosterically regulates channel gating. The allosteric communication pathways between these two heterologus proteins in KATP channels are still poorly understood. This review will highlight the therapeutic agents that target KATP channels and are used to treat diabetes and cardiovascular diseases.

Palabras clave

  • ATP-sensitive potassium channels
  • therapeutic agents
  • diabetes
  • cardiovascular
  • inwardly rectifying potassium channels
  • sulphonylurea receptor
Acceso abierto

Methods for preliminary determination of pemetrexed in macromolecular drug-carrier systems

Publicado en línea: 07 Mar 2016
Páginas: 147 - 153

Resumen

Abstract

Pemetrexed (PMX) is an antifolate drug utilized in the treatment of non-small cell lung cancer. For studies of potential macromolecular carriers for PMX, fast and precise methods were developed to determine the bound and free drug contained in investigated conjugate preparations. The analysis of the total amount of PMX in conjugates was based on absorption spectrophotometry. The linearity was found in the range of 4.697–46.97 μmol L−1 PMX. The limit of quantitation was 1.070 μmol L−1. The method for the analysis of unbound PMX was based on size-exclusion chromatography and detection at 225 nm. This method shows linear range of 2.230–223.0 μmol L−1. LOQ was 0.539 μmol L−1. The proposed methods can be used both for the characterization of the polysaccharide based conjugates of PMX and for the determination of conjugate drug release profiles.

Palabras clave

  • pemetrexed
  • macromolecular drug-carrier
  • size-exclusion chromatography
  • ultraviolet spectroscopy
Acceso abierto

Design and statistical optimization of an effervescent floating drug delivery system of theophylline using response surface methodology

Publicado en línea: 07 Mar 2016
Páginas: 35 - 51

Resumen

Abstract

The aim of this research was to formulate effervescent floating drug delivery systems of theophylline using different release retarding polymers such as ethyl cellulose, Eudragit® L100, xanthan gum and polyethylene oxide (PEO) N12K. Sodium bicarbonate was used as a gas generating agent. Direct compression was used to formulate floating tablets and the tablets were evaluated for their physicochemical and dissolution characteristics. PEO based formulations produced better drug release properties than other formulations. Hence, it was further optimized by central composite design. Further subjects of research were the effect of formulation variables on floating lag time and the percentage of drug released at the seventh hour (D7h). The optimum quantities of PEO and sodium bicarbonate, which had the highest desirability close to 1.0, were chosen as the statistically optimized formulation. No interaction was found between theophylline and PEO by Fourier Transformation Infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) studies.

Palabras clave

  • theophylline
  • gastroretentive
  • floating
  • central composite
  • PEO N12K
Acceso abierto

Simultaneous quantitative analysis of olmesartan, amlodipine and hydrochlorothiazide in their combined dosage form utilizing classical and alternating least squares based chemometric methods

Publicado en línea: 07 Mar 2016
Páginas: 83 - 95

Resumen

Abstract

Simultaneous spectrophotometric analysis of a multi-component dosage form of olmesartan, amlodipine and hydrochlorothiazide used for the treatment of hypertension has been carried out using various chemometric methods. Multivariate calibration methods include classical least squares (CLS) executed by net analyte processing (NAP-CLS), orthogonal signal correction (OSC-CLS) and direct orthogonal signal correction (DOSC-CLS) in addition to multivariate curve resolution-alternating least squares (MCR-ALS). Results demonstrated the efficiency of the proposed methods as quantitative tools of analysis as well as their qualitative capability. The three analytes were determined precisely using the aforementioned methods in an external data set and in a dosage form after optimization of experimental conditions. Finally, the efficiency of the models was validated via comparison with the partial least squares (PLS) method in terms of accuracy and precision.

Palabras clave

  • multivariate calibration methods
  • olmesartan medoxomil
  • amlodipine besylate
  • hydrochlorothiazide
  • spectrophotometry
  • pharmaceutical tablets
Acceso abierto

Optimization of amino acid-stabilized erythropoietin parenteral formulation: In vitro and in vivo assessment

Publicado en línea: 07 Mar 2016
Páginas: 69 - 82

Resumen

Abstract

The aim of this study was to optimize the formulation of erythropoietin (EPO) using amino acids instead of human serum albumin (HSA) and to evaluate its in vivo stability in order to avoid the risk of viral contamination and antigenicity. Different EPO formulations were developed in such a way as to allow studying the effects of amino acids and surfactants on the EPO stability profile. The main techniques applied for EPO analysis were ELISA, Bradford method, and SDS gel electrophoresis. The in vivo stability was evaluated in a Balb-c mouse animal model. The results showed that the presence of surfactant was very useful in preventing the initial adsorption of EPO on the walls of vials and in minimizing protein aggregation. Amino acid combinations, glycine with glutamic acid, provided maximum stability. Formulation F4 (containing glycine, glutamic acid and Tween 20) showed minimum aggregation and degradation and in vivo activity equivalent to commercially available HSA-stabilized EPO (Eprex®).

Palabras clave

  • erythropoietin (EPO)
  • amino acids
  • human serum albumin
  • protein stability
  • Bradford
  • ELISA
  • gel electrophoresis
Acceso abierto

Microscopic methods in analysis of submicron phospholipid dispersions

Publicado en línea: 07 Mar 2016
Páginas: 1 - 22

Resumen

Abstract

Microscopy belongs to the group of tests, used in pharmaceutical technology, that despite the lapse of time and the development of new analytical methods, still remain irreplaceable for the characterization of dispersed drug dosage forms (e.g., suspensions and emulsions). To obtain complete description of a specific drug formulation, such as parenteral colloidal products, a combination of different microscopic techniques is sometimes required. Electron microscopy methods are the most useful ones; however, even such basic methods as optical microscopy may be helpful for determination of some properties of a sample. The publication explicates the most popular microscopical techniques used nowadays for characterization of the morphology of nanoparticles suspended in pharmaceutical formulations; ad vantages and disadvantages of these methods are also discussed. Parenteral submicron formulations containing lecithin or a particular phospholipid were chosen as examples.

Palabras clave

  • optical microscopy
  • electron microscopy
  • AFM
  • phospholipid dispersions
  • parenteral drug delivery systems
Acceso abierto

Physicochemical characterization and dissolution studies of acyclovir solid dispersions with Pluronic F127 prepared by the kneading method

Publicado en línea: 07 Mar 2016
Páginas: 119 - 128

Resumen

Abstract

The dissolution rate of anhydrous acyclovir was improved by the preparation of physical mixtures and solid dispersions with the non-ionic polymer Pluronic F127 using the kneading method at different drug-to-polymer ratios. The obtained physical mixtures and solid dispersions were examined in terms of drug content and possible physical and chemical interactions between the drug and polymer using FTIR spectral studies, differential scanning calorimetry and powder X-ray diffraction analysis. The dissolution rate of acyclovir was determined using the rotating disk method. It was found that the minimal content of the polymer within the mixtures needed to increase the dissolution rate of the drug was 50 %.

Palabras clave

  • acyclovir
  • Pluronic F127
  • solid dispersions
  • physical mixtures
  • kneading
  • dissolution improvement
Acceso abierto

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

Publicado en línea: 07 Mar 2016
Páginas: 129 - 137

Resumen

Abstract

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

Palabras clave

  • guanylhydrazone
  • cytotoxic effect
  • synthesis
  • MTT assay
Acceso abierto

Biphasic dissolution method for quality control and assurance of drugs containing active substances in the form of weak acid salts

Publicado en línea: 07 Mar 2016
Páginas: 139 - 145

Resumen

Abstract

Substances in the form of weak acid salts have been found to be problematic for dissolution testing. Their absorption can start only after they are turned into the form of an acid following the gastric passage although they were administered in the form of a salt. Due to poor solubility, they cannot be tested in acidic gastric environment for a biased dissolution profile. The biphasic dissolution method is promising for overcoming this obstacle. Tablets with warfarin clathrate sodium salt in two concentrations and two different particle size distributions were tested as a suitable model for finding the medium and process conditions of dissolution. The dissolution method based on the use of the upper organic layer (1-octanol) and the lower aqueous layer 0.1 mol L−1 HCl) was found suitable and discriminatory for tablets containing active substances in the form of salts of weak acids. The method also reflects physical differences in the quality of used substances.

Palabras clave

  • weak acid salts
  • warfarin sodium
  • dissolution method
Acceso abierto

Synthesis and structure elucidation of some novel thiophene and benzothiophene derivatives as cytotoxic agents

Publicado en línea: 07 Mar 2016
Páginas: 53 - 68

Resumen

Abstract

Attempting to produce cyclized systems with potential anti-proliferative activity, a series of novel thiophene and benzothiophene derivatives were designed and synthesized. The reactivity of the latter derivatives towards different chemical reagents was studied. Twenty-one compounds were synthesized and evaluated as anti-cancer agents. The results showed that ethyl 5-amino-3-(4-chlorostyryl)-4-cyanothiophene-2-carboxylate (5b), ethyl 5-amino-4-((4-methoxyphenyl)carbonyl)-3-methylhiophene-2-carboxylate (8c) and 5-3-(ethoxy-3-oxopropanamido)-3-methyl-4-(phenylcarbamoyl)thiophene-2-carboxylate (9) were the most active compounds towards three tumor cell lines – MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) and a normal fibro-blast human cell line (WI-38) compared to the anti-proliferative effects of the reference control doxorubicin.

Palabras clave

  • thiophene
  • benzothiophene
  • cytotoxic agents
Acceso abierto

High performance liquid chromatography for simultaneous determination of xipamide, triamterene and hydrochlorothiazide in bulk drug samples and dosage forms

Publicado en línea: 07 Mar 2016
Páginas: 109 - 118

Resumen

Abstract

A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L−1 orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min−1 flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195–100 μg mL−1 for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.

Palabras clave

  • xipamide
  • triamterene
  • hydrochlorothiazide
  • HPLC
  • simultaneous analysis
Acceso abierto

Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo

Publicado en línea: 07 Mar 2016
Páginas: 97 - 107

Resumen

Abstract

The aim of this study was to identify an effective flavonoid that could improve the intracellular accumulation of ritonavir in human brain-microvascular endothelial cells (HBMECs). An in vivo experiment on Sprague-Dawley rats was then designed to further determine the flavonoid’s impact on the pharmacokinetics and tissue distribution of ritonavir. In the accumulation assay, the intracellular leve l of ritonavir was increased in the presence of 25 mmol L−1 of flavonoids in HBMECs. Quercetin showed the strongest effect by improving the intracellular accumulation of ritonavir by 76.9 %. In the pharmacokinetic study, the presence of quercetin in the co-administration group and in the pretreatment group significantly decreased the area under the plasma concentration-time curve (AUC0–t) of ritonavir by 42.2 % (p < 0.05) and 53.5 % (p < 0.01), and decreased the peak plasma concentration (cmax) of ritonavir by 23.1 % (p < 0.05) and 45.8 % (p < 0.01), respectively, compared to the control group (ritonavir alone). In the tissue distribution study, the ritonavir concentration in the brain was significantly increased 2-fold (p < 0.01), during the absorption phase (1 h) and was still significantly higher (p < 0.05) during the distribution phase (6 h) in the presence of quercetin.

Palabras clave

  • quercetin
  • flavonoids
  • ritonavir
  • blood-brain barrier
  • pharmacokinetics
12 Artículos
Acceso abierto

The therapeutic agents that target ATP-sensitive potassium channels

Publicado en línea: 07 Mar 2016
Páginas: 23 - 34

Resumen

Abstract

ATP-sensitive potassium (KATP) channels are a major drug target for the treatment of type-2 diabetes. KATP channels are ubiquitously expressed and link the metabolic state to electrical excitability. In pancreatic β-cells, KATP channels are crucial in the regulation of glucose-induced insulin secretion. Also, KATP channels are involved in the protection against neuronal seizures and ischaemic stress in the heart, brain and in the regulation of vascular smooth muscle tone. Functional KATP channels are hetero-octamers composed of two subunits, a pore forming Kir6, which is a member of the inwardly rectifying potassium channels family, and a regulatory sulphonylurea receptor (SUR). In response to nucleotides and pharmaceutical agonists and antagonists, SUR allosterically regulates channel gating. The allosteric communication pathways between these two heterologus proteins in KATP channels are still poorly understood. This review will highlight the therapeutic agents that target KATP channels and are used to treat diabetes and cardiovascular diseases.

Palabras clave

  • ATP-sensitive potassium channels
  • therapeutic agents
  • diabetes
  • cardiovascular
  • inwardly rectifying potassium channels
  • sulphonylurea receptor
Acceso abierto

Methods for preliminary determination of pemetrexed in macromolecular drug-carrier systems

Publicado en línea: 07 Mar 2016
Páginas: 147 - 153

Resumen

Abstract

Pemetrexed (PMX) is an antifolate drug utilized in the treatment of non-small cell lung cancer. For studies of potential macromolecular carriers for PMX, fast and precise methods were developed to determine the bound and free drug contained in investigated conjugate preparations. The analysis of the total amount of PMX in conjugates was based on absorption spectrophotometry. The linearity was found in the range of 4.697–46.97 μmol L−1 PMX. The limit of quantitation was 1.070 μmol L−1. The method for the analysis of unbound PMX was based on size-exclusion chromatography and detection at 225 nm. This method shows linear range of 2.230–223.0 μmol L−1. LOQ was 0.539 μmol L−1. The proposed methods can be used both for the characterization of the polysaccharide based conjugates of PMX and for the determination of conjugate drug release profiles.

Palabras clave

  • pemetrexed
  • macromolecular drug-carrier
  • size-exclusion chromatography
  • ultraviolet spectroscopy
Acceso abierto

Design and statistical optimization of an effervescent floating drug delivery system of theophylline using response surface methodology

Publicado en línea: 07 Mar 2016
Páginas: 35 - 51

Resumen

Abstract

The aim of this research was to formulate effervescent floating drug delivery systems of theophylline using different release retarding polymers such as ethyl cellulose, Eudragit® L100, xanthan gum and polyethylene oxide (PEO) N12K. Sodium bicarbonate was used as a gas generating agent. Direct compression was used to formulate floating tablets and the tablets were evaluated for their physicochemical and dissolution characteristics. PEO based formulations produced better drug release properties than other formulations. Hence, it was further optimized by central composite design. Further subjects of research were the effect of formulation variables on floating lag time and the percentage of drug released at the seventh hour (D7h). The optimum quantities of PEO and sodium bicarbonate, which had the highest desirability close to 1.0, were chosen as the statistically optimized formulation. No interaction was found between theophylline and PEO by Fourier Transformation Infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) studies.

Palabras clave

  • theophylline
  • gastroretentive
  • floating
  • central composite
  • PEO N12K
Acceso abierto

Simultaneous quantitative analysis of olmesartan, amlodipine and hydrochlorothiazide in their combined dosage form utilizing classical and alternating least squares based chemometric methods

Publicado en línea: 07 Mar 2016
Páginas: 83 - 95

Resumen

Abstract

Simultaneous spectrophotometric analysis of a multi-component dosage form of olmesartan, amlodipine and hydrochlorothiazide used for the treatment of hypertension has been carried out using various chemometric methods. Multivariate calibration methods include classical least squares (CLS) executed by net analyte processing (NAP-CLS), orthogonal signal correction (OSC-CLS) and direct orthogonal signal correction (DOSC-CLS) in addition to multivariate curve resolution-alternating least squares (MCR-ALS). Results demonstrated the efficiency of the proposed methods as quantitative tools of analysis as well as their qualitative capability. The three analytes were determined precisely using the aforementioned methods in an external data set and in a dosage form after optimization of experimental conditions. Finally, the efficiency of the models was validated via comparison with the partial least squares (PLS) method in terms of accuracy and precision.

Palabras clave

  • multivariate calibration methods
  • olmesartan medoxomil
  • amlodipine besylate
  • hydrochlorothiazide
  • spectrophotometry
  • pharmaceutical tablets
Acceso abierto

Optimization of amino acid-stabilized erythropoietin parenteral formulation: In vitro and in vivo assessment

Publicado en línea: 07 Mar 2016
Páginas: 69 - 82

Resumen

Abstract

The aim of this study was to optimize the formulation of erythropoietin (EPO) using amino acids instead of human serum albumin (HSA) and to evaluate its in vivo stability in order to avoid the risk of viral contamination and antigenicity. Different EPO formulations were developed in such a way as to allow studying the effects of amino acids and surfactants on the EPO stability profile. The main techniques applied for EPO analysis were ELISA, Bradford method, and SDS gel electrophoresis. The in vivo stability was evaluated in a Balb-c mouse animal model. The results showed that the presence of surfactant was very useful in preventing the initial adsorption of EPO on the walls of vials and in minimizing protein aggregation. Amino acid combinations, glycine with glutamic acid, provided maximum stability. Formulation F4 (containing glycine, glutamic acid and Tween 20) showed minimum aggregation and degradation and in vivo activity equivalent to commercially available HSA-stabilized EPO (Eprex®).

Palabras clave

  • erythropoietin (EPO)
  • amino acids
  • human serum albumin
  • protein stability
  • Bradford
  • ELISA
  • gel electrophoresis
Acceso abierto

Microscopic methods in analysis of submicron phospholipid dispersions

Publicado en línea: 07 Mar 2016
Páginas: 1 - 22

Resumen

Abstract

Microscopy belongs to the group of tests, used in pharmaceutical technology, that despite the lapse of time and the development of new analytical methods, still remain irreplaceable for the characterization of dispersed drug dosage forms (e.g., suspensions and emulsions). To obtain complete description of a specific drug formulation, such as parenteral colloidal products, a combination of different microscopic techniques is sometimes required. Electron microscopy methods are the most useful ones; however, even such basic methods as optical microscopy may be helpful for determination of some properties of a sample. The publication explicates the most popular microscopical techniques used nowadays for characterization of the morphology of nanoparticles suspended in pharmaceutical formulations; ad vantages and disadvantages of these methods are also discussed. Parenteral submicron formulations containing lecithin or a particular phospholipid were chosen as examples.

Palabras clave

  • optical microscopy
  • electron microscopy
  • AFM
  • phospholipid dispersions
  • parenteral drug delivery systems
Acceso abierto

Physicochemical characterization and dissolution studies of acyclovir solid dispersions with Pluronic F127 prepared by the kneading method

Publicado en línea: 07 Mar 2016
Páginas: 119 - 128

Resumen

Abstract

The dissolution rate of anhydrous acyclovir was improved by the preparation of physical mixtures and solid dispersions with the non-ionic polymer Pluronic F127 using the kneading method at different drug-to-polymer ratios. The obtained physical mixtures and solid dispersions were examined in terms of drug content and possible physical and chemical interactions between the drug and polymer using FTIR spectral studies, differential scanning calorimetry and powder X-ray diffraction analysis. The dissolution rate of acyclovir was determined using the rotating disk method. It was found that the minimal content of the polymer within the mixtures needed to increase the dissolution rate of the drug was 50 %.

Palabras clave

  • acyclovir
  • Pluronic F127
  • solid dispersions
  • physical mixtures
  • kneading
  • dissolution improvement
Acceso abierto

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

Publicado en línea: 07 Mar 2016
Páginas: 129 - 137

Resumen

Abstract

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

Palabras clave

  • guanylhydrazone
  • cytotoxic effect
  • synthesis
  • MTT assay
Acceso abierto

Biphasic dissolution method for quality control and assurance of drugs containing active substances in the form of weak acid salts

Publicado en línea: 07 Mar 2016
Páginas: 139 - 145

Resumen

Abstract

Substances in the form of weak acid salts have been found to be problematic for dissolution testing. Their absorption can start only after they are turned into the form of an acid following the gastric passage although they were administered in the form of a salt. Due to poor solubility, they cannot be tested in acidic gastric environment for a biased dissolution profile. The biphasic dissolution method is promising for overcoming this obstacle. Tablets with warfarin clathrate sodium salt in two concentrations and two different particle size distributions were tested as a suitable model for finding the medium and process conditions of dissolution. The dissolution method based on the use of the upper organic layer (1-octanol) and the lower aqueous layer 0.1 mol L−1 HCl) was found suitable and discriminatory for tablets containing active substances in the form of salts of weak acids. The method also reflects physical differences in the quality of used substances.

Palabras clave

  • weak acid salts
  • warfarin sodium
  • dissolution method
Acceso abierto

Synthesis and structure elucidation of some novel thiophene and benzothiophene derivatives as cytotoxic agents

Publicado en línea: 07 Mar 2016
Páginas: 53 - 68

Resumen

Abstract

Attempting to produce cyclized systems with potential anti-proliferative activity, a series of novel thiophene and benzothiophene derivatives were designed and synthesized. The reactivity of the latter derivatives towards different chemical reagents was studied. Twenty-one compounds were synthesized and evaluated as anti-cancer agents. The results showed that ethyl 5-amino-3-(4-chlorostyryl)-4-cyanothiophene-2-carboxylate (5b), ethyl 5-amino-4-((4-methoxyphenyl)carbonyl)-3-methylhiophene-2-carboxylate (8c) and 5-3-(ethoxy-3-oxopropanamido)-3-methyl-4-(phenylcarbamoyl)thiophene-2-carboxylate (9) were the most active compounds towards three tumor cell lines – MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) and a normal fibro-blast human cell line (WI-38) compared to the anti-proliferative effects of the reference control doxorubicin.

Palabras clave

  • thiophene
  • benzothiophene
  • cytotoxic agents
Acceso abierto

High performance liquid chromatography for simultaneous determination of xipamide, triamterene and hydrochlorothiazide in bulk drug samples and dosage forms

Publicado en línea: 07 Mar 2016
Páginas: 109 - 118

Resumen

Abstract

A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L−1 orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min−1 flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195–100 μg mL−1 for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.

Palabras clave

  • xipamide
  • triamterene
  • hydrochlorothiazide
  • HPLC
  • simultaneous analysis
Acceso abierto

Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo

Publicado en línea: 07 Mar 2016
Páginas: 97 - 107

Resumen

Abstract

The aim of this study was to identify an effective flavonoid that could improve the intracellular accumulation of ritonavir in human brain-microvascular endothelial cells (HBMECs). An in vivo experiment on Sprague-Dawley rats was then designed to further determine the flavonoid’s impact on the pharmacokinetics and tissue distribution of ritonavir. In the accumulation assay, the intracellular leve l of ritonavir was increased in the presence of 25 mmol L−1 of flavonoids in HBMECs. Quercetin showed the strongest effect by improving the intracellular accumulation of ritonavir by 76.9 %. In the pharmacokinetic study, the presence of quercetin in the co-administration group and in the pretreatment group significantly decreased the area under the plasma concentration-time curve (AUC0–t) of ritonavir by 42.2 % (p < 0.05) and 53.5 % (p < 0.01), and decreased the peak plasma concentration (cmax) of ritonavir by 23.1 % (p < 0.05) and 45.8 % (p < 0.01), respectively, compared to the control group (ritonavir alone). In the tissue distribution study, the ritonavir concentration in the brain was significantly increased 2-fold (p < 0.01), during the absorption phase (1 h) and was still significantly higher (p < 0.05) during the distribution phase (6 h) in the presence of quercetin.

Palabras clave

  • quercetin
  • flavonoids
  • ritonavir
  • blood-brain barrier
  • pharmacokinetics

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