Zoltán - István Szabó

University of Medicine and Pharmacy of Târgu Mures | UMFTGM · Drugs Industry and Pharmaceutical Management

Abstract The enantiomers of asenapine maleate (ASN), a novel antipsychotic against schizophrenia and mania with bipolar I disorder have been separated by cyclodextrin (CD) modified capillary zone electrophoresis for the first time. 15 different CDs were screened as complexing agents and chiral selectors, investigating the stability of the inclusion...

The racemic mixture of pomalidomide (POM), a second-generation immunomodulatory uncharged drug, was separated into enantiomers by capillary zone electrophoresis for the first time. Seven different chargeable cyclodextrin (CD) derivatives were screened as complexing agents and chiral selectors, investigating the stability of the POM-CD inclusion com...

Erlotinib (ERL), the anticancer drug of poor bioavailability, was quantified in terms of bio-relevant physicochemical parameters, such as acid–base properties, lipophilicity and solubility, and a comprehensive study on its inclusion complexation was carried out. The protonation constant of ERL (log K = 5.32) indicates that it exists mainly in depro...

Capillary zone electrophoresis employing a dual cyclodextrin (CD) system, consisting of anionic sulfobutylether-β-CD and native β-CD, was developed for the simultaneous chiral separation of four H1-antihistamine racemates (brompheniramine, chlorpheniramine, cetirizine and promethazine). A cost-effective screening using different native and derivati...

A novel stability indicating gradient reverse-phased high-performance liquid chromatographic method has been developed for the quantification of impurities of perindopril tert-butylamine (PER) in pharmaceutical dosage form. Separation of the active substance and its known (Impurities B, C, D, E, F) and unknown impurities was achieved on a BDS Hyper...

Drug repositioning is a high-priority and feasible strategy in the field of oncology research, where the unmet medical needs are continuously unbalanced. Disulfiram is a potential non-chemotherapeutic, adjuvant anticancer agent. However, the clinical translation is limited by the drug`s poor bioavailability. Therefore, the molecular encapsulation o...

This comprehensive review explores the utilization of chiral stationary phases (CSPs) in the context of single-column simultaneous chiral–achiral high-performance liquid chromatography (HPLC) separation methods. While CSPs have traditionally been pivotal for enantioselective drug analysis, contemporary CSPs often exhibit notable chemoselective prop...

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in pol...

An amorphous fiber-based solid dispersion of chlorzoxazone was prepared for the first time by employing centrifugal spinning, using polyvinylpyrrolidone as the fiber-forming polymer. After optimization of the spinning parameters, the obtained fibers were characterized using a set of analytical techniques, both in a solid- and solution-state. Morpho...

Vildagliptin (VIL) is a dipeptidyl peptidase-4 inhibitor used in the treatment of type 2 diabetes mellitus; in therapy, it is available as the enantiomerically pure S-VIL, the other enantiomer R-VIL being considered as an enantiomeric impurity. A systematic screening of 16 cyclodextrin (CD) derivatives as chiral selectors was performed at three pH...

Mechanistic modeling is useful for predicting and modulating selectivity even in early chromatographic method development. This approach is also in accordance with current analytical quality using design principles and is highly welcomed by the authorities. The aim of this study was to investigate the separation behavior of two different types of c...

The chiral separation capability of Chiral-CD-Ph column, containing phenylcarbamate-β-cyclodextrin as the chiral selector in polar organic mode was investigated. A total of twenty-five compounds with different structures and acid–base properties were evaluated, and twenty of them were separated using acetonitrile or methanol as eluent. The effects...

Aceclofenac-loaded polyvinylpyrrolidone fiber-based amorphous solid dispersion was produced successfully by centrifugal spinning. The solution concentration and rotational speed were optimized to produce the fiber-based drug carrier system, with a determined production rate of 12.7 g/h dry solid fibers. The obtained fibers were bead-free and smooth...

The pharmaceutical industry is one of the fastest developing industries, and therefore, the chromatographic methods used to ensure the quality of products are constantly evolving, based on current regulatory requirements. Relevant guidelines state that a good understanding of the effects of all parameters on method performance should be predicted a...

The chiral separation capability of Chiral-CD-Ph column, containing phenylcarbamate-β-cyclodextrin as the chiral selector in polar organic mode was investigated. A total of 25 compounds with different structures and acid-base properties were tested, and 20 of them were separated using acetonitrile or methanol as eluent. The effects of various chrom...

Comparative chiral separations of enantiomeric pairs of four oxazolidinone and two related thio-derivatives were performed by capillary electrophoresis, using cyclodextrins (CDs) as chiral selectors. Since the selected analytes are neutral, the enantiodiscrimination capabilities of nine anionic CD derivatives were determined, in 50 mM phosphate buf...

A new, reversed-phase HPLC (RP-HPLC) method was developed for the simultaneous determination of the dipeptidyl-peptidase-IV-inhibitor antidiabetic drug vildagliptin (VIL) enantiomeric impurity and four other achiral related impurities. An initial screening was performed on five polysaccharide-type chiral stationary phases (Lux Amylose-1, Lux Amylos...

A stereospecific capillary electrophoresis method was developed for the separation of the novel, antipsoriatic agent, apremilast (APR). Six anionic cyclodextrin (CD) derivatives were screened for their ability to discriminate between the uncharged enantiomers. Only succinyl-β-CD (Succ-β-CD) presented chiral interactions; however, the enantiomer mig...

The interaction between human serum albumin (HSA) and apremilast (APR), a novel antipsoriatic drug, was characterized by multimodal analytical techniques including high-performance liquid chromatography (HPLC), fluorescence spectroscopy and molecular docking for the first time. Using an HSA chiral stationary phase, the APR enantiomers were well sep...

Lapatinib (Lap) is a lypophilic drug frequently used in cancer treatment; however, due to its limited solubility and permeability, achieving therapeutic dose through oral administration proves to be a challenge. There are various methods for enhancing the solubility of Lap and other similar drugs, one being the preparation of amorphous solid disper...

A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—of escitalopram. The separation capacity of seven different polysaccharide-type chiral columns, including three amylose-based (Lux Amylose-1, Lux i-Amylose...

Capillary electrophoresis (CE) is a potent method for analyzing chiral substances and is commonly used in the enantioseparation and chiral purity control of pharmaceuticals from different matrices. The adoption of Quality by Design (QbD) concepts in analytical method development, optimization and validation is a widespread trend observed in various...

There are several potential advantages of using experimental design-based retention modelling for chromatographic method development. Most importantly, through the model-delivered systematic understanding (Design Spaces), users can benefit from increased method consistency, flexibility and robustness that can efficiently be achieved at lesser amoun...

A novel, validated, reversed-phase (RP), chiral high performance liquid chromatography (HPLC) method was developed for the enantiopurity control analysis of naproxen, a frequently used non-steroidal anti-inflammatory agent using polysaccharide-type chiral stationary phase (CSP). In the screening phase of method development, seven columns were teste...

Aims: The role of insulin in the regulation of energy metabolism, protein synthesis, proliferation, migration, secretion by keratinocytes, endothelial cells, and fibroblasts suggests that its presence is essential for wound healing (WH). The present study aims to explore the opportunities and limitations of topical insulin (TI) formulations. Method...

The enantioseparation of four phthalimide derivatives (thalidomide, pomalidomide, lenalidomide and apremilast) was investigated on five different polysaccharide-type stationary phases (Chiralpak AD, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) using neat methanol (MeOH), ethanol (EtOH), 1-propanol (PROP), 2-propanol (IPA) and aceto...

The enantioseparation of four oxazolidinone and one biosimilar thiazolidine derivatives was performed on seven different polysaccharide-type chiral stationary phases (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2, Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3, Lux Cellulose-4) differing in backbone (cellulose or amylose), substituent or the imm...

The aim of our research was to prepare polymer-free hydroxypropyl-β-cyclodextrin-(HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) based nanofibers. For this purpose, four-four viscous, aqueous solutions were prepared with different concentrations from each cyclodextrin derivative, with the following concentrations: 170, 180, 190 and 200% (v/w) f...

Fluoxetine hydrochloride is a selective serotonin reuptake inhibitor used in the treatment of depression and obsessive-compulsive disorder. The aim of this study is represented by developing fluoxetineloaded polyvinylpyrrolidone-based fibers by uniaxial electrospinning. The effect of flow rate and needle to collector distance on fiber morphology an...

Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins – differing in cavity size,...

Abstract: Fluoxetine hydrochloride is a selective serotonin reuptake inhibitor used in the treatment of depression and obsessive-compulsive disorder. The aim of this study is represented by developing fluoxetineloaded polyvinylpyrrolidone-based fibers by uniaxial electrospinning. The effect of flow rate and needle to collector distance on fiber mor...

R‐solriamfetol is a recently approved drug used for the treatment of excessive sleepiness associated with narcolepsy and sleep apnea. Herein, a capillary electrophoretic method was developed, enabling the simultaneous analysis of the API and its S‐enantiomer in addition to the enantiomers of its major impurity phenylalaninol. 29 different cyclodext...

Computer-aided ultrahigh performance liquid chromatographic (UHPLC) method development and optimization was undertaken in order to replace an underperforming European Pharmacopoeia method for the determination of albendazole and its related substances. In the preliminary screening, a temperature-gradient time bidimensional model was chosen to aid s...

Scaled-up production of fenofibrate-loaded, polyvinylpyrrolidone-based microfibrous mats was achieved by using corona-electrospinning. An experimental design-based approach was used to study the influence of production parameters on fiber diameter and morphology. Microstructural characterization of the obtained products was performed by scanning el...

Lapatinib-loaded polyvinylpyrrolidone-based nanofibrous solid dispersions were prepared by electrospinning in order to enhance the aqueous solubility and dissolution rate of the anticancer drug. The prepared nanofibers were characterized by smooth-surfaced, homogenous filaments with average diameters of 462±160 nm determined by scanning electron mi...

A reversed-phase high performance liquid chromatographic method was developed and validated for the simultaneous determination of the related substances of S-dapoxetine, including R-dapoxetine, (3S)-3-(dimethylamino-3-phenyl-1-propanol), S-3-amino-3-phenyl-1-propanol, 1-naphtol, 4-phenyl-2H,3H,4H-naphtho[1,2-b]pyran and 1-(2E)-Cinnamyloxynaphthalen...

Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance the dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability. Physicochemical changes that appeared during the electrospinning process were monitored using a wide array of solid-state characterization techniques, including...

Antimicrobial peptides are natural substances that have played a role in the development of the adaptive immune system, and are currently involved in the prevention of infections, through their direct antimicrobial and immunomodulatory properties. While the amino acid composition and spatial structure vary, most antibacterial peptides have a positi...

Solriamfetol is a novel FDA approved enantiopure drug used for the treatment of excessive sleepiness associated with narcolepsy or obstructive sleep apnea. Only the active R-enantiomer is marketed, therefore, a method to determine the chiral purity is essential. Chiral separation of solriamfetol was performed by HPLC using polysaccharide-type chira...

A direct HPLC method was developed for the enantioseparation of pantoprazole using macrocyclic glycopeptide‐based chiral stationary phases, along with various methods to determine the elution order without isolation of the individual enantiomers. In the preliminary screening, four macrocyclic glycopeptide‐based chiral stationary phases containing v...

Aceclofenac-loaded poly(vinyl-pyrrolidone)-based nanofiber formulations were prepared by electrospinning to obtain drug-loaded orally disintegrating webs to enhance the solubility and dissolution rate of the poorly soluble anti-inflammatory active that belongs to the BCS Class-II. Triethanolamine-containing ternary composite of aceclofenac-poly(vin...

A high performance liquid chromatographic method was developed for the simultaneous determination of the related substances (R-ivabradine, dehydro-S-ivabradine, N-demethyl-S-ivabradine, ((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-yl-methyl)-methyl-amine) and 1-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-on-3-yl)-3-chloro-propane)...

Hypertension is considered a major public health issue due to its high prevalence and subsequent risk of cardiovascular and kidney diseases. Thus, the search for new antihypertensive compounds remains of great interest. Snake venoms provide an abundant source of lead molecules that affect the cardiovascular system, which makes them prominent from a...

Novel capillary electrophoresis methods using cyclodextrins (CDs) as chiral selectors were developed and validated for the chiral separation of lansoprazole and rabeprazole, two proton pump inhibitors (PPIs). Fourteen different neutral and anionic CDs were screened at pH 4.0 and 7.0, in the preliminary analysis. Sulfobutyl‐ether‐β‐CD with a degree...

Snake venoms are aqueous solutions containing peptides and proteins with various biochemical, physiological, and pathophysiological effects. Several snake venom components are used as lead molecules in the development of new active substances for the treatment of cardiovascular diseases, clotting disorders, cancer or pain. Antibacterial activity ha...

The chiral separation of three racemic immunomodulatory drugs, thalidomide, pomalidomide and lenalidomide was studied, using three cyclodextrin bonded stationary phases (β-, hydroxypropyl-β- and carboxymethyl-β-CD) in reversed-phase and polar organic mode. In polar organic mode, using acetonitrile and methanol, no chiral separation was observed. In...

Pressure‐assisted stereospecific capillary electrophoresis method was developed for the determination of enantiomeric purity of the antiparkinsonian agent (R)‐rasagiline. The optimized method, 50 mM glycine‐HCl buffer pH 2.0, supplied with 30 mM sulfobutylether‐β‐cyclodextrin, at 35°C, applying 12 kV in reversed polarity, and – 8 mbar pressure (vac...

Enantioseparation of an anti-psoriatic agent, apremilast (APR), was performed by HPLC using polysaccharide-type chiral stationary phases in polar organic mode for the first time. The separation capability of six different chiral columns (Chiralpak AD, Chiralpak IA, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) was investigated using...

A novel, fast and economic chiral HPLC method was developed and validated for the resolution of the four isomers of tofisopam. The separation capacity of eleven different chiral columns: six polysaccharide‐type including three amylose‐based (Chiralpak AD, Chiralpak AD‐RH and Chiralpak AS) and three cellulose‐based (Chiralcel OD, Chiralcel OJ and Lu...

Moxifloxacin (MOX), a novel fourth-generation fluoroquinolone antibacterial was characterized in terms of β-cyclodextrin (β-CD) complexation in order to improve its antibacterial activity. The inclusion complexation has been examined with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR)...

Since technology has had a dramatic impact on healthcare, biomedical engineering techniques gained more and more popularity within biotechnology. The developments in medicine and pharmaceutics and a better understating of proteinprotein interactions pave the way for highly-specific biologics obtained through biosynthesis. Currently, there are more...

Complementary techniques were applied for the investigation of the chiral recognition and enantiomeric resolution of lenalidomide, using various cyclodextrins and polysaccharides as chiral selectors. The high-performance liquid chromatography enantioseparation of the anticancer drug was achieved using polysaccharide-type chiral stationary phases in...

Enantioseparation of the antidiarrheal drug, racecadotril, was investigated by liquid chromatography using polysaccharide-type chiral stationary phases in polar organic mode. The enantiodiscrimininating properties of 4 different chiral columns (Chiralpak AD, Chiralcel OD, Chiralpak AS, Chiralcel OJ) with 5 different solvents (methanol, ethanol, 1-p...

Enantioseparation of nine extensively used chiral pharmaceutical substances from different pharmacological classes and with different structural characteristics has been investigated by capillary zone electrophoresis using Captisol® (sulfobuthylether-β-cyclodextrin sodium salt) as chiral selector. The influence on the chiral separation of several p...

Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state c...

Pediatric, ibuprofen containing orodispersible tablets (ODTs) were prepared using the SeDeM expert system methodology. In order to facilitate formulation, directly compressible ibuprofen was employed (Ibuprofen DC 85™) and characterized using its SeDeM profile. The mannitol based superdisintegrant Ludiflash® was characterized by the SeDeM-ODT exper...

Lapatinib (LAP), the tyrosine kinase inhibitor drug with moderate bioavailability, was characterized in terms of physicochemical properties: acid-base characteristics, lipophilicity, and solubility. The highly lipophilic nature of the drug and its extremely low water solubility ( S0=0.82 nM) limit the development of a parenteral formulation. In ord...

The enantiomers of praziquantel, the drug of choice in schistosomiasis, were separated by electrokinetic chromatography with cyclodextrins. Nine anionic cyclodextrins were screened for their ability to discriminate between the uncharged enantiomers. Seven investigated selectors presented chiral interactions with the enantiomers, these cases being i...

Lapatinib (LAP) the tyrosine kinase inhibitor drug with moderate bioavailability was characterized in terms of physicochemical properties – acid-base characteristics, lipophilicity and solubility. The highly lipophilic nature of the drug and its extremely low water solubility (S0=0.82 nM) limits the development of a parenteral formulation. In order...

Objective: The study aimed at obtaining and characterizing levofloxacin-loaded, poly(ε-caprolactone) electrospun nanofiber formulations to be used as antibacterial wound dressings. Methods: Drug-loaded nanofibers were obtained by the electrospinning process and their morphology was determined using scanning electron microscopy. Structural analysis...

The racemic mixture of thalidomide (THA) has been separated by liquid chromatography using cyclodextrin (CD) bonded stationary phases. Three different chiral columns (β-, hydroxypropyl-β- and carboxymethyl-β-CD) were screened, investigating their enantiodiscriminating capacities. β-CD stationary phase was identified as the most promising one and wa...

Nebivolol-loaded electrospun nanofibrous sheets were prepared for the dissolution enhancement of the active with the aim of improving its oral bioavailability. Physicochemical characterization of nanofibers including differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy and positron annihilation lif...

A sensitive and validated liquid chromatography with mass spectrometry method was developed for the enantioseparation of the racemic mixture of pomalidomide, a novel, second-generation immunomodulatory drug, using β-cyclodextrin-bonded stationary phases. Four cyclodextrin columns (β-, hydroxypropyl-β-, carboxymethyl-β- and sulfobutyl-β-cyclodextrin...

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 tha...

Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although it was demonstrated that the two enantiomers exhibit different pharmacological effects and stereoselective pharmacokinetics. The aim of this study was the evaluation of several native and derivatized cyclodextrines as chiral selectors for the separation of c...

Rheological and microbiological studies were performed for hydrogels prepared with different types of crosslinked polyacrylate polymers (Carbopol® 940, 980 and Ultrez® 10). All hydrogels exhibited typical viscoelastic properties, with no Newtonian flow regimen. Linearizing viscosity profiles, excellent correlations were obtained between logarithmic...

A rapid and simple liquid chromatographic method was developed and validated according to current ICH guidelines for the quantitative assessment of nebivolol from tablet dosage forms and dissolution medium. Chromatography was carried out on a BDS Hypersil C18 column (150 x 4.0 mm, particle size 5 μm), employing a Merck 7000 series HPLC system with...