E-Pub Ahead of Schedule: Bentham Science Publishers are pleased to offer electronic publication of accepted papers prior to scheduled publication. These peer-reviewed papers can be cited using the date of access and the unique DOI number. Any final changes in manuscripts will be made at the time of print publication and will be reflected in the final electronic version of the issue. Articles ahead of schedule may be ordered by pay-per-view at the relevant links by each article stated via the E-Pub Ahead of Schedule.

Disclaimer: Articles appearing in E-Pub Ahead-of-Schedule sections have been peer-reviewed and accepted for publication in this journal and posted online before scheduled publication. Articles appearing here may contain statements, opinions, and information that have errors in facts, figures, or interpretation. Accordingly, Bentham Science Publishers, the editors and authors and their respective employees are not responsible or liable for the use of any such inaccurate or misleading data, opinion or information contained of articles in the E-Pub Ahead-of-Schedule.


Ameliorative Effect of α-Tocopherol and Selenium on Alterations in Liver Biochemical Indices and Hepatic Lesions Induced by Malathion in Rats
Abdulaziz M. Al-Othman, Zeid A. Al-Othman, Gaber E. El-Desoky Karim Yusuf  and Mourad A. M. Aboul-Soud
[Abstract] [FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00042]


Simvastatin: Review of Updates on Recent Trends in Pharmacokinetics, Pharmacodynamics, Drug–drug Interaction, Impurities and Analytical Methods
Pawan Kumar Basniwal and Deepti Jain
[Abstract] [FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00043]


Validation of the Stability-Indicating HPLC Method for the Major Flavonoids in Spray- Dryed Leaf Extract of Aleurites moluccana L. Willd
Talita Gesser Cesca, Luciana Catia Block, Marina Silva Machado, Carolina Wittkowski, Christiane Meyre-Silva, Marcia Maria de Souza, Nara Lins Meira Quintão, Ruth Meri Lucinda Silva, Denise Brentan da Silva,  Eduardo  Fernandes, Leandro de Santis Ferreira, Norberto Peporine Lopes, Valdir Cechinel Filho and Tania Mari Bellé Bresolin
[Abstract] [FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00044]


Optimization of pH and the concentration of parabens in a non-aqueous solution formulation with formation of transesterification reaction products of parabens (alkyl -4-hydroxybenzoates) and glycerin
M. Ilias Jimidar, Roger Embrechts, Urbain Delaet, Willy Peys, Eddy Verhoeven, Tina Arien and Ivo Van Assche
[Abstract] [FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00045]


Complexation of achiral Calixarenes with chiral pharmaceutical substances: a Circular dichroism study
Chamseddin, Chamseddin and Jira, Thomas
[Abstract] [FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00046]



Abstracts


Ameliorative Effect of α-Tocopherol and Selenium on Alterations in Liver Biochemical Indices and Hepatic Lesions Induced by Malathion in Rats
Abdulaziz M. Al-Othman, Zeid A. Al-Othman, Gaber E. El-Desoky Karim Yusuf  and Mourad A. M. Aboul-Soud
[FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00042]

The aim of the present study was to evaluate the potential hepatoprotective effect of α-tocopherol and/or selenium on some plasmatic biochemical indices of liver profile and hepatic damage induced in adult male rats exposed to subchronic dose of malathion (MTN) equivalent to 1/50 LD₅₀. Oral administration of MTN for 45 days significantly induced severe hepatic injury as revealed by increased activity of plasmatic biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) enzymes. Oral administration of α-tocopherol (α-T) and selenium (Se) concomitant with MTN resulted in a significant ameliorative effect by lowering the elevated plasma levels of the previous enzymes. Light microscopic investigation revealed that MTN exposure was associated with necrosis of hepatocytes and marked degenerative changes of liver tissues. Coadministration of (α-T) and Se concomitant with MTN to rats improved the histopathological severity score from severe to normal. However the individual treatment of (α-T) or Se correlated with a relative protection as reflected in the change of the histopathological severity score from severe to mild and moderate, respectively. Thus, it appears that the treatment with (α-T) and/or Se improves MTN hepatotoxicity but is not completely protective.
[Back to top]


Simvastatin: Review of Updates on Recent Trends in Pharmacokinetics, Pharmacodynamics, Drug–drug Interaction, Impurities and Analytical Methods
Pawan Kumar Basniwal and Deepti Jain
[FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00043]

Simvastatin, is a lipid regulating drug, which is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), obtained by synthesis from lovastatin. It is indicated in the treatment of hyperlipidemias, including hypercholesterolaemias, combined mixed hyperlipidemia hyperlipoproteinemias, hypertriglyceridemia, and primary dysbetalipoproteinemia. This review describes a brief overview of the chemistry including impurities and different synthetic schemes, pharmacokinetic, pharmacodynamic and adverse effect of simvastatin as well as the recent trends in drug–drug interaction studies of simvastatin with various drug categories such as antibacterials, anticoagulants, antidepressants, antifungals, antivirals, calcium-channel blockers, immunosuppressants, lipid regulating drugs and grapefruit juice. This review also focuses distinctly on comprehensive update of various analytical methods for the quantification of simvastatin and/or its metabolites, impurities, degradants and other drugs.
[Back to top]


Validation of the Stability-Indicating HPLC Method for the Major Flavonoids in Spray- Dryed Leaf Extract of Aleurites moluccana L. Willd
Talita Gesser Cesca, Luciana Catia Block, Marina Silva Machado, Carolina Wittkowski, Christiane Meyre-Silva, Marcia Maria de Souza, Nara Lins Meira Quintão, Ruth Meri Lucinda Silva, Denise Brentan da Silva,  Eduardo  Fernandes, Leandro de Santis Ferreira, Norberto Peporine Lopes, Valdir Cechinel Filho and Tania Mari Bellé Bresolin
[FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00044]

The HPLC-UV method previously developed for the analysis of the flavonoid 2”-O-rhamnosyl swertisin (I), an active compound of dried leaf extracts of Aleurites moluccana L. Willd, was fully validated with the inclusion of another flavonoid, swertisin (II). The stability-indicating capability of the method was established by analyzing forced degradation extract samples (acid, alkali, neutral, oxidative and photolytic condition) in which the spectral purity of the markers was ascertained together with the separation of degradation products from the markers. The method proved be linear over a range of 5.89-117.8 and 1.38-27.68 mg.mL-1 for I and II, respectively. The recovery for I and II was 100.3 and 102.8%, respectively, at a level of 100%. A relative standard deviation (RSD%) < 1.0% (intra-day) and < 3.5% (inter-days) for area, and less than 0.5% for retention time indicated that the precision of the method is acceptable. Validation parameters such as selectivity and robustness were also determined. In addition, during the course of LC-MSn analysis three other flavonoids were discovered in the A. moluccana extract and their tentative structures identified.
[Back to top]


Optimization of pH and the concentration of parabens in a non-aqueous solution formulation with formation of transesterification reaction products of parabens (alkyl -4-hydroxybenzoates) and glycerin
M. Ilias Jimidar, Roger Embrechts, Urbain Delaet, Willy Peys, Eddy Verhoeven, Tina Arien and Ivo Van Assche
[FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00045]

The formation of trans-esterification byproducts of methyl- and propylparaben with glycerin was observed during formulation of an oral solution drug product.

To obtain a stable product that is physically, chemically and microbial stable during storage at room temperature conditions, the pH of the formulation and the concentration level of the parabens were optimized meticulously to obtain a robust manufacturing process.

An HPLC method was developed and fully validated for the determination of methyl- and propylparaben in the formulation. The method was able to detect the levels of the transesterifcation byproducts as well. Typical validation parameters such as accuracy, precision, and linearity, etc. were assessed, along with demonstration of the robustness, stability of solution, evaluation of forced degradation studies and setting of system suitability tests and criteria.
[Back to top]


Complexation of achiral Calixarenes with chiral pharmaceutical substances: a Circular dichroism study
Chamseddin, Chamseddin and Jira, Thomas
[FULL-TEXT INQUIRY] [BSP/CPA/E-Pub/00046]

Calixarenes (CAs), with their unique three-dimensional surface, are one of the best known host molecules along with cyclodextrins, and crown ethers.  However, these compounds have been less studied compared to cyclodextrins. The present work is devoted to the evaluation of the ability of eleven different calixarenes to form host-guest complexes with eleven pharmaceutical relevant substances (chiral active pharmaceutical ingredients/APIs) in different solutions (acetonitrile, methanol and water), including comparisons between water-soluble calixarenes and three pharmaceutically relevant cyclodextrins (α-, β- and γ-cyclodextrins) by means of circular dichroism spectroscopy (CD). The obtained CD spectra provided the absolute configuration of the chiral APIs, as well as of the interactions with host-molecules. An attempt to understand the complexation mechanism of calixarenes was undertaken based on the CD-spectra of the drugs with different host macrocycles. These results indicate that calixarenes could serve as candidate host molecules in the pharmaceutical researches due to their versatility and the ease of adding different moieties to their upper and/or lower rim, which makes it easier to change the affinity of these cyclooligomers towards target molecules and/or increase the solubility of the calixarenes.
[Back to top]