Concentration Dependent Single Chain Properties of Poly(Sodium 4-Styrenesulfonate) Subjected to Aromatic Interactions with Chlorpheniramine Maleate Studied by Diafiltration and Synchrotron-SAXS

The polyelectrolyte poly(sodium 4-styrenesulfonate) undergoes aromatic–aromatic interaction with the drug chlorpheniramine, which acts as an aromatic counterion. In this work, we show that an increase in the concentration in the dilute and semidilute regimes of a complex polyelectrolyte/drug 2:1 produces the increasing confinement of the drug in hydrophobic domains, with implications in single chain thermodynamic behavior. Diafiltration analysis at polymer concentrations between 0.5 and 2.5 mM show an increase in the fraction of the aromatic counterion irreversibly bound to the polyelectrolyte, as well as a decrease in the electrostatic reversible interaction forces with the remaining fraction of drug molecules as the total concentration of the system increases. Synchrotron-SAXS results performed in the semidilute regimes show a fractal chain conformation pattern with a fractal dimension of 1.7, similar to uncharged polymers. Interestingly, static and fractal correlation lengths increase with increasing complex concentration, due to the increase in the amount of the confined drug. Nanoprecipitates are found in the range of 30–40 mM, and macroprecipitates are found at a higher system concentration. A model of molecular complexation between the two species is proposed as the total concentration increases, which involves ion pair formation and aggregation, producing increasingly confined aromatic counterions in hydrophobic domains, as well as a decreasing number of charged polymer segments at the hydrophobic/hydrophilic interphase. All of these features are of pivotal importance to the general knowledge of polyelectrolytes, with implications both in fundamental knowledge and potential technological applications considering aromatic-aromatic binding between aromatic polyelectrolytes and aromatic counterions, such as in the production of pharmaceutical formulations.

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Contribution to the Detection of Poor Quality Sildenafil Drugs in Burkina Faso Using High-Performance Thin-Layer Chromatography

Journal of Analytical Methods in Chemistry ◽

10.1155/2021/4093859 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Abdoul Karim Sakira ◽

Mitéhélé Sandrine Marie Josiane Ouattara ◽

Moussa Yabre ◽

Moumouni Bande ◽

Touridomon Issa Some

Keyword(s):

Burkina Faso ◽

High Performance ◽

Pharmaceutical Formulations ◽

Poor Quality ◽

Counterfeit Drugs ◽

Drug Molecules ◽

Validity Range ◽

Optimization Parameters ◽

Peak Areas ◽

Layer Chromatography

In substandard drugs enforcement, there is a need to develop reliable, fast, and inexpensive analytical methods. Due to its very characteristics, HPTLC offers opportunities for the development of methods that meet these requirements. This technique was used to develop and validate a method for the determination of sildenafil in pharmaceutical formulations from the licit and illicit supply chain in Burkina Faso. Taking into account optimization parameters such as measurement wavelength and mobile phase composition, the best elution quality is found at the maximum signals of spots on silica plates at 305 nm, using a mixture of dichloromethane-methanol mixture 9 : 1 (v/v) proportions. The method developed under these conditions was validated using the accuracy profile as a decision tool. The establishment of the response function curves allowed the choice of the polynomial function applied to the peak areas. This mathematical model provides a validity range between 0.4 and 0.6 mg/mL. The application of the developed and validated method to collected samples allowed the detection of two substandard drugs and confirmed the poor quality of drugs in the illicit market. More data using this approach in a variety of drug molecules could lead to the establishment of databases of counterfeit drugs in Burkina Faso.

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MX-type single chain complexes with an aromatic in-plane ligand: incorporation of aromatic interactions for stabilizing the chain structure

Dalton Transactions ◽

10.1039/c9dt00784a ◽

2019 ◽

Vol 48 (22) ◽

pp. 7828-7834 ◽

Cited By ~ 2

Author(s):

Unjila Afrin ◽

Hiroaki Iguchi ◽

Mohammad Rasel Mian ◽

Shinya Takaishi ◽

Hiromichi Yamakawa ◽

...

Keyword(s):

Chain Structure ◽

Single Chain ◽

One Dimensional ◽

Aromatic Interactions ◽

Chain Complexes ◽

First Time

MX-type one-dimensional complexes containing only an aromatic in-plane ligand were synthesized for the first time.

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Rapid, Precise and Affordable Estimation of Venlafaxine and Its Metabolites in Highly Polluted Effluent Waters: Proof-of-Concept for Methodology

Molecules ◽

10.3390/molecules25204793 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4793

Author(s):

Snawar Hussain ◽

Chandramouli Ramnarayanan ◽

Teeka S. Roopashree ◽

Md. Khalid Anwer ◽

Nagaraja Sreeharsha ◽

...

Keyword(s):

Analytical Method ◽

Antidepressant Drug ◽

Colorimetric Method ◽

Parent Drug ◽

Pharmaceutical Formulations ◽

Effluent Treatment ◽

Long Term Effects ◽

Drug Molecules ◽

Pharmacologically Active

Widespread presence of pharmaceuticals and their metabolites in the environment of industrialized countries is an emerging global concern. Potential contamination of the soil and water by such pharmacologically active substances poses serious ecotoxicological implications. Several studies assessing the long-term ecological risks of pharmaceutical contaminants mainly focus on the risk assessment of the parent drug, while the potential contributions of their metabolites is often neglected. Presence of selective serotonin and norepinephrine reuptake inhibitor venlafaxine, an antidepressant drug, and its metabolites is a matter of serious concern for aquatic systems, since they are difficult to remove by traditional wastewater treatment processes. The concentration of VEN present in water is reportedly one of the highest among pharmaceuticals; however, the long-term effects of its metabolites have not yet been systematically studied. Given the consideration to complex and time-consuming effluent treatment, and realizing the importance of levels of venlafaxine and its metabolites, a simple and accurate analytical method for quick determination is needed. We designed a selective colorimetric method by using oxidative coupling of drug molecules with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) reagent, to quantify the presence of venlafaxine and its metabolites in aquatic samples, with special emphasis on effluent. The method was validated for selectivity, specificity and robustness as per the ICH Q2 guidelines to assess its suitability in pharmaceutical samples, as well. Highly sensitive and green economical analytical method was successfully established for estimation of venlafaxine and its metabolites in aquatic samples. The method was quick, as it involved minimum processing steps. The method was accurate and linear in the range of 0.5 to 80 ppm and could successfully detect lowest concentration of 1.3 ppm, thus qualifying its applicability for the desired purpose to check the presence of trace levels of VEN or its metabolites in aquatic samples or in pharmaceutical formulations.

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Degradative transport of cationic amphiphilic drugs across phospholipid bilayers

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2006.1842 ◽

2006 ◽

Vol 364 (1847) ◽

pp. 2597-2614 ◽

Cited By ~ 45

Author(s):

Magdalena Baciu ◽

Sarra C Sebai ◽

Oscar Ces ◽

Xavier Mulet ◽

James A Clarke ◽

...

Keyword(s):

Drug Transport ◽

Single Chain ◽

Drug Molecules ◽

Cationic Amphiphilic Drugs ◽

Amphiphilic Drugs ◽

Multiple Cell ◽

Ester Linkage ◽

Significant Mechanism ◽

Hydrolysis Of

Drug molecules must cross multiple cell membrane barriers to reach their site of action. We present evidence that one of the largest classes of pharmaceutical drug molecules, the cationic amphiphilic drugs (CADs), does so via a catalytic reaction that degrades the phospholipid fabric of the membrane. We find that CADs partition rapidly to the polar–apolar region of the membrane. At physiological pH, the protonated groups on the CAD catalyse the acid hydrolysis of the ester linkage present in the phospholipid chains, producing a fatty acid and a single-chain lipid. The single-chain lipids rapidly destabilize the membrane, causing membranous fragments to separate and diffuse away from the host. These membrane fragments carry the drug molecules with them. The entire process, from drug adsorption to drug release within micelles, occurs on a time-scale of seconds, compatible with in vivo drug diffusion rates. Given the rate at which the reaction occurs, it is probable that this process is a significant mechanism for drug transport.

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Complexation of Cyclodextrins with Benzoic Acid in Water-Organic Solvents: A Solvation-Thermodynamic Approach

Molecules ◽

10.3390/molecules26154408 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4408

Author(s):

Tatyana R. Usacheva ◽

Vitaly A. Volynkin ◽

Viktor T. Panyushkin ◽

Dmitry A. Lindt ◽

Thi Lan Pham ◽

...

Keyword(s):

Complex Formation ◽

Gibbs Energy ◽

Benzoic Acid ◽

Molecular Complex ◽

Pharmaceutical Formulations ◽

Solvent Mixture ◽

Thermodynamic Approach ◽

Molecular Complex Formation ◽

Molecular Complexation ◽

The Stability

The aim of this research is to obtain new data about the complexation between β-cyclodextrin (β-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. This research may help developing cyclodextrin-based pharmaceutical formulations through the choice of the appropriate solvent mixture that may be employed in the industrial application aiming to control the reactions/processes in liquid phase. In this paper, NMR results for the molecular complex formation between BA and β-CD ([BA⊂β-CD]) in D2O-DMSO-d6 and in D2O-EtOH have shown that the stability of the complex in the H2O-DMSO-d6 varies within the experimental error, while decreases in H2O-EtOH. Changes in the Gibbs energy of BA resolvation in water and water–dimethylsulfoxide mixtures have been obtained and have been used in the analysis of the reagent solvation contributions into the Gibbs energy changes of the [BA⊂β-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between β-CD and BA as well as the structure of the [BA⊂β-CD] complex and the energy of β-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA⊂β-CD] complex in H2O-EtOH and H2O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA⊂β-CD] molecular complexation as well as the reagent solvation contributions in H2O-EtOH and H2O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.

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Stability-indicating High-performance liquid chromatography method for simultaneous determination of aminophylline and chlorpheniramine maleate in pharmaceutical formulations

Indian Journal of Pharmaceutical Sciences ◽

10.4103/0250-474x.169042 ◽

2015 ◽

Vol 77 (5) ◽

pp. 515 ◽

Cited By ~ 7

Author(s):

M Ahmed ◽

A Ali ◽

T Mahmud ◽

MA Qadir ◽

K Nadeem ◽

...

Keyword(s):

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

Simultaneous Determination ◽

High Performance ◽

Pharmaceutical Formulations ◽

Chlorpheniramine Maleate ◽

Chromatography Method ◽

Stability Indicating ◽

Liquid Chromatography Method

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Near-infrared chemical imaging for quantitative analysis of chlorpheniramine maleate and distribution homogeneity assessment in pharmaceutical formulations

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545816500024 ◽

2016 ◽

Vol 09 (06) ◽

pp. 1650002 ◽

Cited By ~ 2

Author(s):

Manfei Xu ◽

Luwei Zhou ◽

Qiao Zhang ◽

Zhisheng Wu ◽

Xinyuan Shi ◽

...

Keyword(s):

Near Infrared ◽

Spatial Information ◽

Nir Spectroscopy ◽

Pharmaceutical Formulations ◽

Chemical Imaging ◽

Hyperspectral Data ◽

Data Cube ◽

Chemical Information ◽

Chlorpheniramine Maleate ◽

Homogeneity Assessment

Near infrared chemical imaging (NIR-CI) combines conventional near infrared (NIR) spectroscopy with chemical imaging, thus provides spectral and spatial information simultaneously. It could be utilized to visualize the spatial distribution of the ingredients in a sample. The data acquired using NIR-CI instrument are hyperspectral data cube (hypercube) containing thousands of spectra. Chemometric methodologies are necessary to transform spectral information into chemical information. Partial least squares (PLS) method was performed to extract chemical information of chlorpheniramine maleate in pharmaceutical formulations. A series of samples which consisted of different CPM concentrations (w/w) were compressed and hypercube data were measured. The spectra extracted from the hypercube were used to establish the PLS model of CPM. The results of the model were [Formula: see text] 0.981, RMSEC 0.384%, RMSECV 0.483%, RMSEP 0.631%, indicating that this model was reliable.

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Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.010727 ◽

2020 ◽

Vol 295 (17) ◽

pp. 5640-5653 ◽

Cited By ~ 1

Author(s):

Aaron G. Bart ◽

Kurt L. Harris ◽

Elizabeth M. J. Gillam ◽

Emily E. Scott

Keyword(s):

Cytochrome P450 ◽

Active Site ◽

Substrate Selectivity ◽

Cytochrome P450 Enzymes ◽

Drug Molecules ◽

Structural Evaluation ◽

Aromatic Interactions ◽

Open Conformation ◽

17Β Estradiol ◽

Variable Substrate

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.

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Special Issue: Advanced Materials in Drug Release and Drug Delivery Systems

Materials ◽

10.3390/ma14041042 ◽

2021 ◽

Vol 14 (4) ◽

pp. 1042

Author(s):

Katarzyna Winnicka

Keyword(s):

Drug Delivery ◽

Pharmaceutical Industry ◽

Drug Release ◽

Drug Delivery Systems ◽

Pharmaceutical Formulations ◽

Delivery Systems ◽

Advanced Materials ◽

Special Issue ◽

New Drug ◽

Drug Molecules

Development of new drug molecules is costly and requires longitudinal, wide-ranging studies; therefore, designing advanced pharmaceutical formulations for existing and well-known drugs seems to be an attractive device for the pharmaceutical industry [...]

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