Revista y Edición

Volumen 72 (2022): Edición 3 (September 2022)

Volumen 72 (2022): Edición 2 (June 2022)

Volumen 72 (2022): Edición 1 (March 2022)

Volumen 71 (2021): Edición 4 (December 2021)

Volumen 71 (2021): Edición 3 (September 2021)

Volumen 71 (2021): Edición 2 (June 2021)

Volumen 71 (2021): Edición 1 (March 2021)

Volumen 70 (2020): Edición 4 (December 2020)

Volumen 70 (2020): Edición 3 (September 2020)

Volumen 70 (2020): Edición 2 (June 2020)

Volumen 70 (2020): Edición 1 (March 2020)

Volumen 69 (2019): Edición 4 (December 2019)

Volumen 69 (2019): Edición 3 (September 2019)

Volumen 69 (2019): Edición 2 (June 2019)

Volumen 69 (2019): Edición 1 (March 2019)

Volumen 68 (2018): Edición 4 (December 2018)

Volumen 68 (2018): Edición 3 (September 2018)

Volumen 68 (2018): Edición 2 (June 2018)

Volumen 68 (2018): Edición 1 (March 2018)

Volumen 67 (2017): Edición 4 (December 2017)

Volumen 67 (2017): Edición 3 (September 2017)

Volumen 67 (2017): Edición 2 (June 2017)

Volumen 67 (2017): Edición 1 (March 2017)

Volumen 66 (2016): Edición 4 (December 2016)

Volumen 66 (2016): Edición 3 (September 2016)

Volumen 66 (2016): Edición 2 (June 2016)

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

Volumen 65 (2015): Edición 4 (December 2015)

Volumen 65 (2015): Edición 3 (September 2015)

Volumen 65 (2015): Edición 2 (June 2015)

Volumen 65 (2015): Edición 1 (March 2015)

Volumen 64 (2014): Edición 4 (December 2014)

Volumen 64 (2014): Edición 3 (September 2014)

Volumen 64 (2014): Edición 2 (June 2014)

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

Volumen 63 (2013): Edición 4 (December 2013)

Volumen 63 (2013): Edición 3 (September 2013)

Volumen 63 (2013): Edición 2 (June 2013)

Volumen 63 (2013): Edición 1 (March 2013)

Volumen 62 (2012): Edición 4 (December 2012)

Volumen 62 (2012): Edición 3 (September 2012)

Volumen 62 (2012): Edición 2 (June 2012)

Volumen 62 (2012): Edición 1 (March 2012)

Volumen 61 (2011): Edición 4 (December 2011)

Volumen 61 (2011): Edición 3 (September 2011)

Volumen 61 (2011): Edición 2 (June 2011)

Volumen 61 (2011): Edición 1 (March 2011)

Volumen 60 (2010): Edición 4 (December 2010)

Volumen 60 (2010): Edición 3 (September 2010)

Volumen 60 (2010): Edición 2 (June 2010)

Volumen 60 (2010): Edición 1 (March 2010)

Volumen 59 (2009): Edición 4 (December 2009)

Volumen 59 (2009): Edición 3 (September 2009)

Volumen 59 (2009): Edición 2 (June 2009)

Volumen 59 (2009): Edición 1 (March 2009)

Volumen 58 (2008): Edición 4 (December 2008)

Volumen 58 (2008): Edición 3 (September 2008)

Volumen 58 (2008): Edición 2 (June 2008)

Volumen 58 (2008): Edición 1 (March 2008)

Volumen 57 (2007): Edición 4 (December 2007)

Volumen 57 (2007): Edición 3 (September 2007)

Volumen 57 (2007): Edición 2 (June 2007)

Volumen 57 (2007): Edición 1 (March 2007)

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 2 (June 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

Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents

Publicado en línea: 28 May 2016
Páginas: 155 - 171

Resumen

Abstract

As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6–20, acrylamide 21, thiazolidine 22, thiazoles 23–29 and thiophenes 33–35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27–45 μmol L–1) compared to doxorubicin (IC50 47.9 μmol L–1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin.

Palabras clave

  • quinolines
  • pyridine
  • thienopyridine
  • isoquinoline
  • acrylamide
  • thiazole
  • thiophene
  • anticancer activity
Acceso abierto

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system

Publicado en línea: 28 May 2016
Páginas: 173 - 189

Resumen

Abstract

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained.

Palabras clave

  • pulsatile release
  • chronopharmaceutical system
  • piecewise function
  • design of experiment
  • Eudragit RS
  • metoprolol
Acceso abierto

Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design

Publicado en línea: 28 May 2016
Páginas: 191 - 206

Resumen

Abstract

To evaluate the influence of different variables on tablet formulations containing enalapril maleate and indapamide as active substances, two separate experimental designs were employed: one for evaluating powder properties and the other for tablet characteristics. Because of the low active pharmaceutical ingredient content, it was hypothesized that both powder and tablet properties could be determined only by the characteristics of excipients. In order to test this assumption, both experimental designs were done with placebo mixtures. The optimized formulation was then evaluated both with and without APIs. Results indicated that filler and lubricant percentage, along with compression force, were the most important variables during the formulation study. The optimized formulation showed similar characteristics in both cases for all responses, except for angle of repose and friability where only minor differences were observed. The combination of the applied approaches (using placebo composition and fractional experimental design) proved to be efficient, cost effective and time saving.

Palabras clave

  • design of experiments
  • optimization
  • factorial design
  • placebo formulation
Acceso abierto

The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process

Publicado en línea: 28 May 2016
Páginas: 207 - 218

Resumen

Abstract

Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content).

Palabras clave

  • salmon calcitonin
  • inhalation
  • spray freeze drying
  • hydroxypropyl-β-cyclodextrin
  • fine particle fraction
  • stability
Acceso abierto

Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus

Publicado en línea: 28 May 2016
Páginas: 219 - 231

Resumen

Abstract

New derivatives of 2-thiobenzimidazole incorporating triazole moiety were synthesized, characterized and tested in vitro for antiviral activity against hepatitis C virus (HCV) and hepatitis B virus (HBV). Their cytotoxicity was determined by the reduction in the number of viable cell. All of the synthesized compounds are inactive against HBV and some showed activity against HCV. In particular, two compounds showed significant activity, 2-{4-[(1-benzoylbenzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitro-phenyl)-acetamide (13) and 2-(4-{[1-(p-chlorobenzoyl)-benzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitrophenyl)-acetamide (17). The results give an insight into the importance of the substituent at position 2 of benzimidazole for the inhibition of HCV.

Palabras clave

  • benzimidazole
  • triazole
  • anilide
  • antiviral
  • HCV
  • HBV
Acceso abierto

Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats

Publicado en línea: 28 May 2016
Páginas: 233 - 244

Resumen

Abstract

Centella asiatica was extracted by methanol. The assay content of triterpenes in the extract was 0.12 % asiatic acid, 0.54 % madecassic acid, 0.25 % asiaticoside and 1.02 % madecassoside. The extract was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) and formulated with Eudragit E100, glycerol, PEG 400, copovidone, ethanol and purified water. A clear yellowish solution (F1-F8) was obtained. The formulations had a pH of 5.5–6.0 with viscosity in the range of 20–60 mPa s, surface tension 20.3–24.6 mN m–1 and contact angle less than 20°. The amount of PEG 400 and copovidone affected the film and spreadability. The content of triterpenes in the spray formulation was close to 100 % compared to triterpenes in the extract. The skin irritation study indicated that the formulation was non-irritating in a rat model. An in vivo excision wound healing model showed that wound excision was completely healed after 14 days.

Palabras clave

  • extract
  • hydroxypropyl--cyclodextrin
  • wound healing
  • topical spray
Acceso abierto

Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

Publicado en línea: 28 May 2016
Páginas: 245 - 256

Resumen

Abstract

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

Palabras clave

  • dental pain
  • mucoadhesion time
  • mucoadhesive strength
  • buccal tablet
  • artificial neural network
Acceso abierto

Coated pellets with delayed-release glucose for prevention of hypoglycemic episodes

Publicado en línea: 28 May 2016
Páginas: 257 - 267

Resumen

Abstract

Patients tend to prevent hypoglycemia by excessive saccharide intake leading to poorer glycemic control with potentially fatal consequences. This problem could be resolved by means of pellets with glucose release delayed by 120–360 min as a compensation of the antidiabetic drug peak effect. No glucose is released before; hence there is no risk of hyperglycemia and secondary complications. The pellets contain glucose in combination with an osmotically active ingredient and are coated with an ethylcellulose dispersion, which forms an insoluble semipermeable membrane and ensures delayed release. The release of glucose was assessed using dissolution and high-performance liquid chromatography. Dissolution profiles indicated the possibility of achieving the requested lag time using a combination of adequate compositions and coating concentrations. Lag times of 60, 240 and 360 min were achieved. The sample containing carboxymethyl starch was found to be most suitable for the intent of this work.

Palabras clave

  • hypoglycemia
  • diabetes mellitus
  • pellets
  • delayed release
  • glucose
  • pellet evaluation
Acceso abierto

Release of selected amino acids from zinc carriers

Publicado en línea: 28 May 2016
Páginas: 269 - 277

Resumen

Abstract

The paper deals with the results of an investigation of the release of selected amino acids (histidine, tryptophan, tyrosine) from model suspensions prepared by co-precipitation with zinc chloride. It has been proven that the influence of the Zn(II)/amino acid molar ratio on dissolution profiles of the tested amino acids and dissolution half-life (t1/2) of histidine or tryptophan is significant. The amount of amino acid in the dispersed phase (supporting dose) is a determinant of the amino acid release profile. There is a minimal supporting dose (30.0 μmol of histidine or 17.4 μmol of tryptophan) that provides release of similar amounts of amino acid (4.1–4.6 μmol of histidine or 8.7–9.9 μmol of tryptophan) after the same time intervals. The tyrosine release profiles follow first order kinetics since the supporting dose (0.9–11.2 μmol) is limited by the tyrosine low solubility in water.

Palabras clave

  • amino acids
  • zinc
  • suspensions
  • dissolution
  • kinetics
Acceso abierto

Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs

Publicado en línea: 28 May 2016
Páginas: 279 - 287

Resumen

Abstract

A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least.

Palabras clave

  • -oxiracetam
  • -oxiracetam
  • conformation
  • pharmacokinetics
  • beagle dogs
Acceso abierto

Optimized genotyping method for identification of bacterial contaminants in pharmaceutical industry

Publicado en línea: 28 May 2016
Páginas: 289 - 295

Resumen

Abstract

Microbiological control is of crucial importance in the pharmaceutical industry regarding the possible bacterial contamination of the environment, water, raw materials and finished products. Molecular identification of bacterial contaminants based on DNA sequencing of the hypervariable 16SrRNA gene has been introduced recently. The aim of this study is to investigate the suitability of gene sequencing using our selection of PCR primers and conditions for rapid and accurate bacterial identification in pharmaceutical industry quality control.

DNA was extracted from overnight incubated colonies from 10 bacterial ATCC strains, which are common contaminants in the pharmaceutical industry. A region of bacterial 16SrRNA gene was analyzed by bidirectional DNA sequencing. Bacterial identification based on partial sequencing of the 16SrRNA gene is the appropriate method that could be used in the pharmaceutical industry after adequate validations. We have successfully identified all tested bacteria with more than 99 % similarity to the already published sequences.

Palabras clave

  • 16rRNA
  • genotyping
  • bacterial identification
  • pharmaceutical industry
Acceso abierto

Effect of rutin from tartary buckwheat sprout on serum glucose-lowering in animal model of type 2 diabetes

Publicado en línea: 28 May 2016
Páginas: 297 - 302

Resumen

Abstract

This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; it is negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down-regulation of serum glucose level in type 2 diabetes.

Palabras clave

  • tartary buckwheat sprout
  • rutin
  • type 2 diabetes
  • insulin signaling
12 Artículos
Acceso abierto

Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents

Publicado en línea: 28 May 2016
Páginas: 155 - 171

Resumen

Abstract

As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6–20, acrylamide 21, thiazolidine 22, thiazoles 23–29 and thiophenes 33–35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27–45 μmol L–1) compared to doxorubicin (IC50 47.9 μmol L–1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin.

Palabras clave

  • quinolines
  • pyridine
  • thienopyridine
  • isoquinoline
  • acrylamide
  • thiazole
  • thiophene
  • anticancer activity
Acceso abierto

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system

Publicado en línea: 28 May 2016
Páginas: 173 - 189

Resumen

Abstract

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained.

Palabras clave

  • pulsatile release
  • chronopharmaceutical system
  • piecewise function
  • design of experiment
  • Eudragit RS
  • metoprolol
Acceso abierto

Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design

Publicado en línea: 28 May 2016
Páginas: 191 - 206

Resumen

Abstract

To evaluate the influence of different variables on tablet formulations containing enalapril maleate and indapamide as active substances, two separate experimental designs were employed: one for evaluating powder properties and the other for tablet characteristics. Because of the low active pharmaceutical ingredient content, it was hypothesized that both powder and tablet properties could be determined only by the characteristics of excipients. In order to test this assumption, both experimental designs were done with placebo mixtures. The optimized formulation was then evaluated both with and without APIs. Results indicated that filler and lubricant percentage, along with compression force, were the most important variables during the formulation study. The optimized formulation showed similar characteristics in both cases for all responses, except for angle of repose and friability where only minor differences were observed. The combination of the applied approaches (using placebo composition and fractional experimental design) proved to be efficient, cost effective and time saving.

Palabras clave

  • design of experiments
  • optimization
  • factorial design
  • placebo formulation
Acceso abierto

The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process

Publicado en línea: 28 May 2016
Páginas: 207 - 218

Resumen

Abstract

Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content).

Palabras clave

  • salmon calcitonin
  • inhalation
  • spray freeze drying
  • hydroxypropyl-β-cyclodextrin
  • fine particle fraction
  • stability
Acceso abierto

Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus

Publicado en línea: 28 May 2016
Páginas: 219 - 231

Resumen

Abstract

New derivatives of 2-thiobenzimidazole incorporating triazole moiety were synthesized, characterized and tested in vitro for antiviral activity against hepatitis C virus (HCV) and hepatitis B virus (HBV). Their cytotoxicity was determined by the reduction in the number of viable cell. All of the synthesized compounds are inactive against HBV and some showed activity against HCV. In particular, two compounds showed significant activity, 2-{4-[(1-benzoylbenzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitro-phenyl)-acetamide (13) and 2-(4-{[1-(p-chlorobenzoyl)-benzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitrophenyl)-acetamide (17). The results give an insight into the importance of the substituent at position 2 of benzimidazole for the inhibition of HCV.

Palabras clave

  • benzimidazole
  • triazole
  • anilide
  • antiviral
  • HCV
  • HBV
Acceso abierto

Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats

Publicado en línea: 28 May 2016
Páginas: 233 - 244

Resumen

Abstract

Centella asiatica was extracted by methanol. The assay content of triterpenes in the extract was 0.12 % asiatic acid, 0.54 % madecassic acid, 0.25 % asiaticoside and 1.02 % madecassoside. The extract was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) and formulated with Eudragit E100, glycerol, PEG 400, copovidone, ethanol and purified water. A clear yellowish solution (F1-F8) was obtained. The formulations had a pH of 5.5–6.0 with viscosity in the range of 20–60 mPa s, surface tension 20.3–24.6 mN m–1 and contact angle less than 20°. The amount of PEG 400 and copovidone affected the film and spreadability. The content of triterpenes in the spray formulation was close to 100 % compared to triterpenes in the extract. The skin irritation study indicated that the formulation was non-irritating in a rat model. An in vivo excision wound healing model showed that wound excision was completely healed after 14 days.

Palabras clave

  • extract
  • hydroxypropyl--cyclodextrin
  • wound healing
  • topical spray
Acceso abierto

Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

Publicado en línea: 28 May 2016
Páginas: 245 - 256

Resumen

Abstract

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

Palabras clave

  • dental pain
  • mucoadhesion time
  • mucoadhesive strength
  • buccal tablet
  • artificial neural network
Acceso abierto

Coated pellets with delayed-release glucose for prevention of hypoglycemic episodes

Publicado en línea: 28 May 2016
Páginas: 257 - 267

Resumen

Abstract

Patients tend to prevent hypoglycemia by excessive saccharide intake leading to poorer glycemic control with potentially fatal consequences. This problem could be resolved by means of pellets with glucose release delayed by 120–360 min as a compensation of the antidiabetic drug peak effect. No glucose is released before; hence there is no risk of hyperglycemia and secondary complications. The pellets contain glucose in combination with an osmotically active ingredient and are coated with an ethylcellulose dispersion, which forms an insoluble semipermeable membrane and ensures delayed release. The release of glucose was assessed using dissolution and high-performance liquid chromatography. Dissolution profiles indicated the possibility of achieving the requested lag time using a combination of adequate compositions and coating concentrations. Lag times of 60, 240 and 360 min were achieved. The sample containing carboxymethyl starch was found to be most suitable for the intent of this work.

Palabras clave

  • hypoglycemia
  • diabetes mellitus
  • pellets
  • delayed release
  • glucose
  • pellet evaluation
Acceso abierto

Release of selected amino acids from zinc carriers

Publicado en línea: 28 May 2016
Páginas: 269 - 277

Resumen

Abstract

The paper deals with the results of an investigation of the release of selected amino acids (histidine, tryptophan, tyrosine) from model suspensions prepared by co-precipitation with zinc chloride. It has been proven that the influence of the Zn(II)/amino acid molar ratio on dissolution profiles of the tested amino acids and dissolution half-life (t1/2) of histidine or tryptophan is significant. The amount of amino acid in the dispersed phase (supporting dose) is a determinant of the amino acid release profile. There is a minimal supporting dose (30.0 μmol of histidine or 17.4 μmol of tryptophan) that provides release of similar amounts of amino acid (4.1–4.6 μmol of histidine or 8.7–9.9 μmol of tryptophan) after the same time intervals. The tyrosine release profiles follow first order kinetics since the supporting dose (0.9–11.2 μmol) is limited by the tyrosine low solubility in water.

Palabras clave

  • amino acids
  • zinc
  • suspensions
  • dissolution
  • kinetics
Acceso abierto

Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs

Publicado en línea: 28 May 2016
Páginas: 279 - 287

Resumen

Abstract

A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least.

Palabras clave

  • -oxiracetam
  • -oxiracetam
  • conformation
  • pharmacokinetics
  • beagle dogs
Acceso abierto

Optimized genotyping method for identification of bacterial contaminants in pharmaceutical industry

Publicado en línea: 28 May 2016
Páginas: 289 - 295

Resumen

Abstract

Microbiological control is of crucial importance in the pharmaceutical industry regarding the possible bacterial contamination of the environment, water, raw materials and finished products. Molecular identification of bacterial contaminants based on DNA sequencing of the hypervariable 16SrRNA gene has been introduced recently. The aim of this study is to investigate the suitability of gene sequencing using our selection of PCR primers and conditions for rapid and accurate bacterial identification in pharmaceutical industry quality control.

DNA was extracted from overnight incubated colonies from 10 bacterial ATCC strains, which are common contaminants in the pharmaceutical industry. A region of bacterial 16SrRNA gene was analyzed by bidirectional DNA sequencing. Bacterial identification based on partial sequencing of the 16SrRNA gene is the appropriate method that could be used in the pharmaceutical industry after adequate validations. We have successfully identified all tested bacteria with more than 99 % similarity to the already published sequences.

Palabras clave

  • 16rRNA
  • genotyping
  • bacterial identification
  • pharmaceutical industry
Acceso abierto

Effect of rutin from tartary buckwheat sprout on serum glucose-lowering in animal model of type 2 diabetes

Publicado en línea: 28 May 2016
Páginas: 297 - 302

Resumen

Abstract

This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; it is negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down-regulation of serum glucose level in type 2 diabetes.

Palabras clave

  • tartary buckwheat sprout
  • rutin
  • type 2 diabetes
  • insulin signaling

Planifique su conferencia remota con Sciendo