Search

Valentina Buda,1,* Minodora Andor,2,* Carmen Cristescu,1,* Mirela Cleopatra Tomescu,2 Danina M Muntean,3 Dana Emilia Bâibâță,4,5 Diana Aurora Bordejevic,4,5 Corina Danciu,6 Olivia Dalleur,7 Dorina Coricovac,8 Zorin Crainiceanu,9 Anca Tudor,10 Ionut Ledeti,11 Lucian Petrescu4,5 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 2Department of Medical Semiotics, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 3Department of Pathophysiology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 4Department of Cardiology VI, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 5Cardiovascular Diseases Institute, Timisoara 300310, Romania; 6Department of Pharmacognosy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 7Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Woluwe-Saint-Lambert 1200, Bruxelles, Belgium; 8Department of Toxicology, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 9Department of Plastic and Reconstructive Surgery, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 10Department of Statistics and Biomedical Informatics, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 11Department of Physical Chemistry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania*These authors contributed equally to this workCorrespondence: Valentina BudaCorina Danciu Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, Timisoara 300041, RomaniaTel +40-256-494-604Fax +40-256-494-604Email buda.valentina.oana@gmail.comBackground: Thrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension.Materials and methods: Here, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties).Results: After one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p

Valentina Buda,1,* Minodora Andor,2,* Dana Emilia Baibata,3,4,* Ramona Cozlac,3,4 Gabriela Radu,2 Dorina Coricovac,5 Corina Danciu,6 Ionut Ledeti,7 Adelina Cheveresan,8 Cristian Nica,9 Paul Tuduce,10 Mirela Cleopatra Tomescu21Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 2Department of Medical Semiotics, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 3Department of Cardiology VI, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 4Cardiovascular Diseases Institute, Timisoara, Romania; 5Department of Toxicology, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 6Department of Pharmacognosy, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 7Department of Physical Chemistry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 8Department of Pharmacology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 9Department of Surgery, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 10Department of Balneophysiotherapy, Rheumatology and Rehabilitation, Faculty of Medicine, Vasile Goldis Western University, Arad, Romania*These authors contributed equally to this work Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction.Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage.Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p

The present article is aimed towards the structural NMR analysis of 4H-4-amino- 3-mercapto-5-(4-pyridil)-1,2,4-triazole (3) and its product of alkylation (via sodium salt) with ethyl chloroacetate in absolute ethanol. 4H-4-amino-3-mercapto-5-(4-pyridil)-1,2,4- triazole and 4H-4-amino-5-ethoxycarbonyl-methylsulfanyl-3-(4-pyridil)-1,2,4-triazole (4) were characterized by IR, ¹H-NMR, 13C-NMR spectroscopy and structures were elucidated by 2D-1H-13C-HMBC spectroscopy. [ABSTRACT FROM AUTHOR]

Syntheses of novel metal complexes of Cd2+ and Cu2+ was carried out in aqueous solution, using CdI2 and CuCl2·2H2O as source for metal ions and sodium salt of 4H-4- amino-5-carboxymethylsulfanyl-3-phenyl-1,2,4-triazole as ligand. All the compounds were preliminary characterized by melting point and IR spectroscopy. [ABSTRACT FROM AUTHOR]

Zofenopril calcium (ZOF)is one of the newest angiotensin converting enzyme (ACE) inhibitor, is one of the highly lipophilic newest angiotensin and with low water solubility. This research investigates the interaction between ZOF and a β-cyclodextrin chemically modified derivative, 2-hydroxypropyl-β-cyclodextrin (HPBCD), in order to prove the formation of an inclusion complex with an enhanced water solubility profile of ZOF. In this research is reported for the first time the physicochemical characterization and the solubility profile of an inclusion complex between ZOF and HPBCD. Different spectroscopic techniques (UV absorption spectrometry, powder X-ray diffraction, attenuated total reflectance Fourier transform IR spectroscopy) were applied in order to prove the formation of the ZOF/HPBCD inclusion complex, both in water and in solid state, backed by thermal analysis (TGA/DTG/HF). The obtained results confirm that the physicochemical properties of the ZOF/HPBCD binary system, prepared using the kneading method, are different in comparison both with the parent substances and the corresponding physical mixture, thus suggesting that an inclusion complex was formed. After the formation of the inclusion complex with HPBCD, the solubility test indicated that the water solubility of ZOF was increased by 5 times.

Abstract Background Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition. Results New improved extraction methods were applied on the bark of Betula pendula in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and 13C NMR spectroscopy which revealed a very high yield of betulin (over 90%). Growth inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma), HeLa (cervix adenocarcinoma) and MCF7 (breast adenocarcinoma), by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice. Conclusions The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.

A new metal complex containing Zn(II) as complex generator and active substance methotrexate (MTX) as ligand was obtained. The coordinative compound was characterized by means of thermogravimetric analysis, complexometry and elemental analysis.It was proved that in the experimental conditions a compound was obtained with molar ration Zn(II):MTX = 1:2. As the thermal stability may be crucial to assessing applicability of new compounds, the thermal behavior of the complex is discussed in detail comparative with the one of the ligand. The spectroscopic data suggest that the methotrexate acts as ligand toward the metal cation of Zn. The TG-DTG and DSC curves show for the Zn(II) complex the dehydration process occurs in two consecutive steps and the thermal decomposition of the anhydrous compound takes place in a continuous process composed of two significant steps. This fact is sustained by the different Eα values function of α, the result being interpreted as overlapping reactions with a complex mechanism. [ABSTRACT FROM AUTHOR]

TG/DTG and Heat Flow (HF) data were used to determine the thermal parameters of methotrexate - active substance and tablets. A tablet with 2.5 mg active substance was analysed. The TG curves of MTX active substance and tablet displayed three and five thermal decomposition processes, respectively. Analysis of the HF data showed some interactions between methotrexate active substance and the excipients of tablets, suggested by alterations in the melting point of methotrexate and the modification of enthalpies of melting value (?H), but these interactions are not confirmed by the FTIR analysis. [ABSTRACT FROM AUTHOR]

Angiotensin II receptor antagonists are tetrazole derivatives used in the treatment of high blood pressure, and are also indicated for the treatment of heart failure (NYHA class II-IV). They are used alone or in combination with other classes of antihypertensives or diuretics for the effective management of high blood pressure. In this study, we aim to evaluate the thermal stability and degradation kinetics for the principal compounds used in therapy from this class, namely telmisartan, valsartan, olmesartan medoxomil, and losartan potassium. To obtain the thermoanalytical data for the kinetic investigations, the TG and DTG curves were registered at five different heating rates (β = 2, 4, 6, 8, and 10 °C min -1 ). The kinetic methods used were a preliminary ASTM E698 method and two isoconversional methods: Flynn-Wall-Ozawa and Friedman. For each molecule, the results showed complex decomposition processes consisting of complex reaction sequences.

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest-host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole-cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.

The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials-ASTM E698, Friedman and Flynn-Wall-Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.

In this paper, the thermal stability of pure l-thyroxine (THY) and l-thyroxine sodium salt hydrate (THYSS) vs. two pharmaceutical solid formulations commercialized on both Romanian and European market (with a content of 100μg, respectively 200μg THYSS per tablet) were investigated. In order to determine whether the presence of excipients affects the thermal stability of the active pharmaceutical ingredient (API), the preliminary study of thermal stability in air atmosphere was completed with an in-depth solid-state kinetic study. By kinetic analysis, the non-isothermal degradation of the selected active pharmaceutical ingredients vs. the solid formulation with strength of 200μg THYSS per tablet was investigated. Isoconversional methods (Kissinger-Akahira-Sunose, Flynn-Wall-Ozawa and Friedman) were employed for the estimation of activation energies values, at five different heating rates, β=5, 7, 10, 12 and 15°Cmin(-1). Also, a fourth method was applied in the processing of data, namely NPK, allowing an objective separation in the physical and chemical processes that contribute to the thermal degradation of the selected compounds. A discussion of thermal stability from the kinetic point of view is also presented., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Betulonic acid belongs to the pentacyclic triterpenic derivative class and can be obtained through the selective oxidation of betulin. In this study we set obtaining several functionalized derivatives of this compound by its condensation with several amino compounds such as aminoguanidine, hydroxylamine, n-butylamine and thiosemicarbazide as our goal. The functionalization of the parent compound led to several molecules with antiproliferative potential, the most promising being 3-2-carbamothioylhydrazonolup-20(29)-en-28-oic acid.

This paper reports on the synthesis and characterization of two Schiff bases bearing 1,2,4-triazolic moieties, namely 4H-4-(2-hydroxy-benzylidene-amino)-5-benzyl-3-mercapto-1,2,4-triazole and 4H-4-(4-nitro-benzylidene-amino)-5-benzyl-3-mercapto-1,2,4-triazole using thin layer chromatography, melting interval, elemental analysis, spectroscopy and thermal stability studies.

Background: The compatibility study of active substances with excipients finds an important role in the domain of pharmaceutical research, being known the fact that final formulation is the one administered to the patient. In order to evaluate the compatibility between active substance and excipients, different analytical techniques can be used, based on their accuracy, reproducibility and fastness., Results: Compatibility study of two well-known active substances, procaine and benzocaine, with four commonly used excipients, was carried out employing thermal analysis (TG/DTG/HF) and Fourier Transform Infrared Spectroscopy (UATR-FT-IR). The selected excipients were microcrystalline cellulose, lactose monohydrate, magnesium stearate and talc. Equal proportion of active substance and excipients (w/w) was utilized in the interaction study. The absolute value of the difference between the melting point peak of active substances and the one corresponding for the active substances in the analysed mixture, as well the absolute value of the difference between the enthalpy of the pure active ingredient melting peak and that of its melting peak in the different analysed mixtures were chosen as indexes of the drug-excipient interaction degree. All the results obtained through thermal analysis were also sustained by FT-IR spectroscopy., Conclusions: The corroboration of data obtained by thermal analysis with the ones from FT-IR spectroscopy indicated that no interaction occurs between procaine and benzocaine, with microcrystalline cellulose and talc, as well for the benzocaine-lactose mixture. Interactions were confirmed between procaine and benzocaine respectively and magnesium stearate, and for procaine and lactose.

In this work, the thermal behaviour of three active substances (phenazone, aminophenazone, phenylbutazone) was studied by drawing up the TG/DTG/DTA curves in air/nitrogen atmosphere at 10 °C min(-1) heating rate. The information on the thermal-induced events was corroborated with the IR spectra of the solid samples (pharmaceutical compounds and the remaining chars after heating treatment), respectively with the ones obtained by evolved gases analysis (EGA). The data on a possible drug-excipient interaction were obtained from the thermoanalytical study of mixtures of these active compounds with talc, magnesium stearate, starch and microcrystalline cellulose. No changes were observed by TG/DTG/DTA curves of mixtures in comparison with the pure compound. Even if the three active substances contain the same heterocyclic ring, having similar molecular structures, their thermal behaviour is not similar. According to thermal and evolved gas analysis, it was proved that formation of CO₂ does not involve atmospheric oxygen. By stoichiometric means, the molecular breakdown of aminophenazone can generate only carbon monoxide, which undergoes disproportionation, generating CO₂., (Copyright © 2013 Elsevier B.V. All rights reserved.)