Category Archives: Original Research

Preparation and Characterization of Levofloxacin-Loaded Nanofibers as Potential Wound Dressings

Noémi Pásztor, Emőke Rédai, Zoltán-István Szabó, Emese Sipos

University of Medicine and Pharmacy of Tîrgu Mureș, Romania

DOI: 10.1515/amma-2017-0014

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 of the prepared nanofibers was carried out using differential scanning calorimetry and dissolution testing was performed in order to determine drug release.
Results: Both nanofiberous formulations (containing 20 % and 50 % w/w levofloxacin) showed dimensions in the range of few hundred nanometers. Thermograms indicated that the formulation containing 20% levofloxacin was totally amorphized, showing a rapid release of the active, in 20 minutes.
Conclusions: The poly(ε-caprolactone)-based electrospun nanofibers, containing levofloxacin presented suitable characteristics for obtaining potential antibacterial wound dressings.

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Short Period Storage Impact on Bioactive Constituents from Bilberries and Blueberries

Ruxandra Emilia Ştefănescu1, Sigrid Eșianu2, Eszter Laczkó-Zöld2, Anca Mare3, Bianca Tudor3, Maria Titica Dogaru4

1 University of Medicine and Pharmacy Tîrgu Mureș
2 University of Medicine and Pharmacy Tîrgu Mureș, Faculty of Pharmacy, Department of Pharmacognosy and Phytotherapy
3 University of Medicine and Pharmacy Tîrgu Mureș, Faculty of Medicine, Department of Microbiology, Virology, and Parasitology
4 University of Medicine and Pharmacy Tîrgu Mureș, Faculty of Pharmacy, Department of Pharmacology and Clinical Pharmacy

DOI: 10.1515/amma-2017-0010

Objectives: The aim of this study was to assess storage effects on anthocyanin and total polyphenol content in different bilberry and blueberry extracts and to evaluate the antioxidant and antibacterial activity of these extracts.
Materials and methods: Total phenolic content, total monomeric anthocyanin content and antioxidant activity were determined in the first month and after three months storage of berries at either -20 °C or -50 °C. Two different solvents were used (methanol and 50% ethanol). Antibacterial activity was determined for the 3 months stored fruits using a microdilution method and was expressed as the minimum inhibitory concentration.
Results: There were significant differences between the concentration in the first month and after three months storage in both types of fruit extracts. Regarding the extracting solvent, we noticed that total phenols were better extracted with 50% ethanol, while the total monomeric anthocyanin content was higher in the methanolic extracts. No significant or slightly significant differences were observed between the fruits stored at -20 °C or -50 °C. Ethanolic extracts showed the highest scavenging activity. Good antibacterial activity was observed on gram-positive bacteria.
Conclusions: Storage conditions are an important factor that can influence chemical composition of fruits. Although freezing is a good option for preservation, our study showed a high decrease in the concentration of total phenols and anthocyanins after only three months. The fruits have shown a high antioxidant activity and a good antibacterial effect. Further studies are needed for better understanding the changes that can appear during the storage.

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Evaluation of Mechanical Properties of Nonsteroidal Anti-Inflammatory Matrix Type Transdermal Therapeutic Systems

Paula Antonoaea1, Nicoleta Todoran1, Emőke Rédai1, Adriana Ciurba1, Cătălina Bogdan2, Mirela Moldovan2, Daniela Lucia Muntean3

1 Department of Pharmaceutical Technology, University of Medicine and Pharmacy of Tîrgu Mureș, Romania
2 Department of Dermatopharmacy and Cosmetics, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
3 Department of Analytical Chemistry and Drug Analysis, University of Medicine and Pharmacy of Tîrgu Mureș, Romania

DOI: 10.1515/amma-2017-0011

Objective: Transdermal therapeutic systems (TTSs) represent an intensely studied alternative to oral delivery of non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of rheumatic diseases due to its ability of avoiding the side effects of the oral route. This study aims to present the evaluation of the mechanical properties of three NSAIDs (meloxicam, tenoxicam and indomethacin) individually included in four type of polymeric matrixes, as part of new formulations development process.
Methods: 12 products in form of TTS matrixes were prepared by solvent casting evaporation technique, using hydroxypropyl methylcellulose (HPMC 15000, HPMC E5) and/or ethylcellulose as matrix-forming polymers. Each of the resulted products was evaluated by determining the water vapor absorption, desorption or transmission in controlled atmosphere humidity (evaluation of porosity); the elongation capacity, tensile strength and bioadhesiveness (evaluation of mechanical properties).
Results: The analysis of three groups of the experimental data expressed as averages on each group was necessary, in order to identify the parameters which statistically are critically influenced by the ingredients associated in the TTSs matrix compositions. Analysis by normality tests, variance and correlation tests (Anova, Pearson) enabled evaluation of the effect of NSAID type vs. the effect of polymer matrix type on the parameters of the NSAID TTS matrix.
Conclusions: Meloxicam incorporated in the structure of HPMC 15000 polymeric matrix favors its viscoelastic structure. Ethylcellulose functions as plasticizer and supports the matrix bioadhesiveness. HPMC E5 does not meet the requirements for TTS preparation in the used experimental conditions.

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The Influence of Some Parameters on Chiral Separation of Ibuprofen by High-Performance Liquid Chromatography and Capillary Electrophoresis

Alina Balint, Anca Gabriela Cârje*, Daniela Lucia Muntean, Silvia Imre

Department of Analytical Chemistry and Drug Analysis, University of Medicine and Pharmacy Tîrgu Mures, Romania

DOI: 10.1515/amma-2017-0009

Objective: The aim of the study was to compare the influence of mobile phase composition and temperature on chiral separation of racemic ibuprofen by capillary electrophoresis and high performance liquid chromatography with UV detection.
Materials and methods: Racemic ibuprofen was analysed on a chiral OVM column with an HPLC system 1100 Agilent Technologies, under isocratic elution, by using potassium dihydrogen phosphate 20 mM and ethanol in mobile phase. The flow rate was set at 1 mL/min, UV detector at 220 nm and different column temperatures were tested. For electrophoresis separation an Agilent CE G1600AX Capillary Electrophoresis System system, with UV detection, was used. The electrophoresis analysis was performed at different pH values and temperatures, with phosphate buffer 25 mM and methyl-β-cyclodextrin as chiral selector.
Results: The chromatograhic analysis reveals a high influence of mobile phase pH on ibuprofen enantiomers separation. An elution with a mixture of potassium dihydrogen phosphate 20 mM pH=3 and ethanol, at 25ºC, allowed enantiomers separation with good resolution in less than 8 min.
Conclusions: The proposed HPLC method proved suitable for the separation of ibuprofen enantiomers with a good resolution, but the capillary electrophoresis tested parameters did not allow chiral discrimination.

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Relationship Between High Levels of Salivary Cotinine Test and Demographic Characteristics of Pregnant Smokers from Mures County

Ion Mihai Georgescu1, Monica Tarcea2, Claudiu Marginean3, Florina Ruta2, Victoria Rus2, Remus Sipos4, Zoltan Abram1

1 Department of Hygiene, University of Medicine and Pharmacy Tirgu Mures
2 Department of Community Nutrition, University of Medicine and Pharmacy Tirgu Mures
3 Department of Obstetrics and Gynecology I, County Emergency Hospital Tirgu Mures
4 Department of Anatomy, University of Medicine and Pharmacy TirguMures; Mures county General Practitioners Association

DOI: 10.1515/amma-2017-0008

Objectives: To evaluate the relationship between the frequency of self-declared status regarding smoking in a group of pregnant women from Mures county, Romania and the high levels of Salivary Cotinine (SC) like biomarkers.
Material and methods: It was conducted a retrospective study among 230 pregnant women presented for prenatal care at 50 General Practitioners cabinets in Mures county, Romania, in 2015. Data were collected with a validated questionnaire which included age, level of education, socioeconomic status and ethnicity, also the self-reported smoking status. The Salivary Cotinine level was evaluated using NicAlert Saliva test kits.
Results: Using salivary test we identified a high prevalence of involuntary exposure to cigarette smoke among both non-smokers and those who quit smoking before pregnancy. Also we registered pregnant women that although declared smoking cessation before pregnancy their salivary Cotinine levels were high, almost like to an active smoker, probably because of second-hand exposure or because they didn’t say the truth about their habit.
Conclusions: We underline the importance of implementing more efficient community interventions among this vulnerable group in order to reduce the frequency of smoking and sustain quitting.

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Precursor Synthesis of Some New Macrocyclic Compounds

Șerban Andrei Gâz-Florea1, Eleonora Mircia2, Lavinia Berţa (Grama)3

1 Organic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy Tîrgu Mureş, Romania
2 Drugs Industry and Pharmaceutical Management Department, Faculty of Pharmacy, University of Medicine and Pharmacy Tîrgu Mureş, Romania
3 General and Inorganic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy Tîrgu Mureş, Romania

DOI: 10.1515/amma-2017-0005

Objective: Development of new electronic devices with applications in computer science as well as new medical devices pushed the researcher to find new technologies. Based on those new techniques we have designed and synthesized compounds with possible application in the field of advanced materials.
Material and method: Compounds were analyzed by TLC and NMR. Routine 1H NMR (250 MHz) spectra were recorded at room temperature in deuterated acetone, unless stated otherwise. Thin-layer chromatography (TLC) was carried out on aluminum sheets coated with silicagel 60 F254 Merck TLC plates.
Results: Starting from commercial available compounds intermediates were obtained in a good yield. 4,4′-(2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-diyl)diphenol was obtained starting from pentaerythritol and p-hydroxy-benzaldehyde in the presence of catalytic amounts of APTS (p-toluensulfonic acid). The product was purified by recrystallization and characterized by NMR spectroscopy. The structure exhibit 2 different signals for equatorial and axial position. Furthermore di, tri and tetra ethylene glycol were obtained by microwave assisted synthesis in a matter of minutes. Compounds were separated by recrystallization.
Conclusions: In conclusion, several intermediates were synthesized and characterized from spectroscopic point of view. Further analyses should be carried out and the compounds should be tested as advanced materials.

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Kinetics and Mechanism of Drug Release from Loratadine Orodispersible Tablets Developed without Lactose

Adriana Ciurba, Emőke Rédai, Ioana Pop, Paula Antonoaea, Nicoleta Todoran

University of Medicine and Pharmacy Tirgu Mures, Romania

DOI: 10.1515/amma-2017-0004

Objective: The aim of this study is to develop lactose-free orodispersible tablets with loratadine for patients with lactose intolerance.
Materials and methods: Seven compositions (F1-F7) of 10 mg loratadine were prepared in form of orally disintegrating tablets, by direct compression, using croscarmellose sodium and pre-gelatinized starch in various concentrations as superdisintegrants, diluted with microcrystalline cellulose and combined with mannitol and maltodextrin as binder agents. The tablets had been studied in terms of their pharmacotechnical characteristics, by determining: the weight uniformity of the tablets, their friability, breaking strength and disintegration time, drug content and the dissolution profile of loratadine. The statistical analyses were performed with GraphPad Prism Software Inc. As dependent variables, both the hardness of the tablets and their disintegration ability differ between batches due to their compositional differences (as independent variables). DDSolver were used for modeling the kinetic of the dissolution processes by fitting the dissolution profiles with time-dependent equations (Zero-order, First-order, Higuchi, Korsmeyer-Peppas, Peppas-Sahlin).
Results: All proposed formulas shows rapid disintegration, in less than 15 seconds, and the dissolution loratadine spans a period of about 10 minutes. Akaike index as well as R2 adjusted parameter have demonstrated that the studied dissolution profiles are the best fitted by Zero-order kinetic.
Conclusion: In conclusion, association of croscarmellose sodium (7.5%) with pre-gelatinized starch (6%) as superdisintegrants and mannitol as the binder agent (35%), positively influences the dissolution properties of loratadine from orally fast dispersible tablets.

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Characteristics of Sleep Apnea Assessed Before Discharge in Patients Hospitalized with Acute Heart Failure

Ildikó Kocsis1, Lajos Fehérvári1, Zoltán Fogarasi2, István Adorján Szabó1, Attila Frigy1*

1 University of Medicine and Pharmacy Tirgu Mures, Romania
2 Clinical County Hospital Tirgu Mures, Romania

DOI: 10.1515/amma-2017-0003

Objectives. Evaluation of the characteristics of sleep apnea (SA) in patients hospitalized with acute heart failure, considering that undiagnosed SA could contribute to early rehospitalization.
Methods. 56 consecutive patients (13 women, 43 men, mean age 63.12 years) with acute heart failure, in stable condition, underwent nocturnal polygraphy before hospital discharge. The type and severity of SA was determined. Besides descriptive statistics, correlations between the severity of SA and clinical and paraclinical characteristics were also analyzed (t-test, chi-square test, significancy at alpha < 0.05).
Results. 12 (21.4%) subjects were free of SA (AHI – apnea-hipopnea index <5/h), 15 (26.7%) had mild SA (AHI=5-14/h), 17 (30.3%) had moderate SA (AHI 15-30/h), and 12 (21.4 %) had severe SA (AHI>30/h). The apnea was predominantly obstructive (32 cases vs. 12 with central SA). Comparing the patients with mild or no SA with those with severe SA, we did not find statistically significant correlations (p>0.05) between the severity of SA and the majority of main clinical and paraclinical characteristics – age, sex, BMI, cardiac substrates of heart failure, comorbidities. Paradoxically, arterial hypertension (p=0.028) and atrial fibrillation (p=0.041) were significantly more prevalent in the group with mild or no SA.
Conclusions. Before discharge, in the majority of patients hospitalized with acute heart failure moderate and severe SA is present, and is not related to the majority of patient related factors. Finding of significant SA in this setting is important, because its therapy could play an important role in preventing readmissions and improving prognosis.

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The Prevalence of Dysphotopsia in Patients with Recent Cataract Surgery

Andreea Dana Fişuş1*, Zoltán Madaras1, Karin Ursula Horváth1,2

1 Tîrgu Mureş County Hospital, Ophthalmology Clinic
2 University of Medicine and Pharmacy Tîrgu Mureş

DOI: 10.1515/amma-2017-0002

Pseudophakic dysphotopsia are becoming increasingly important as unwanted side effect after cataract surgery. Objective: The purpose of this study is to compare the photic symptoms experienced by patients after cataract surgery.
Material and method: This is a prospective study that included 105 eyes from 99 patients, which underwent uncomplicated phacoemulsification and IOL implantation, between June 2015 and June 2016, performed at Ophthalmology Clinic Tg Mureș. Patients without visually consequential ocular co-morbidity completed a questionnaire, designed to assess subjectively perceived visual functioning and identify symptoms of dysphotopsia.
Results: From the total number of patient, hydrophobic lenses were implanted in 95 patients and 10 patients received hydrophilic lenses. Photic effects were reported in 18% of treated eyes. Although the percentage of dysphotopsia is higher in the hydrophobic lenses category, there was no significant statistical difference between the two categories.
Conclusion: The incidence and significance should not be overlooked, thus visual acuity is not enough for evaluating postoperative visual function.

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Comparative Analysis of Hepcidin-25 and Inflammatory Markers in Patients with Chronic Kidney Disease with and without Anemia

Carmen Denise Căldăraru1, Dorin Ionuţ Tarta1*, Mirela Liana Gliga1, Cristina Tarta2, Emilian Caraşca3, Sorin Albu3, Adina Huţanu4,5, Maria Dogaru6, Grigore Dogaru1

1 Department of Nephrology, University of Medicine and Pharmacy of Targu Mures, Romania
2 Department of Internal Medicine, County Clinical Hospital Targu- Mures, Romania
3 Department of Internal Medicine, University of Medicine and Pharmacy of Targu Mures, Romania
4 CCAMF of University of Medicine and Pharmacy of Targu Mureș, Romania
5 Department of Laboratory Medicine, University of Medicine and Pharmacy of Targu Mureș, Romania
6 Department of Pharmacology, University of Medicine and Pharmacy of Targu Mureș, Romania

DOI: 10.1515/amma-2017-0001

Introduction: Hepcidin is a regulatory protein in iron metabolism; we do not know the role in chronic kidney disease anemia.
Methods: 22 patients with CKD anemia and 15 patients with CKD without anemia were investigated. CKD anemia-inclusion criteria: over 18 years, hemoglobin ≤12 g/dl for women and ≤13 g/dl for men, no treatment for anemia 6 months before enrollment, glomerular filtration rate (eGFR) <60 ml/min/1.73m² and stable creatinine three months before enrollment. Exclusion criteria: infection, bleeding, malignancy, systemic or liver disease, immunosuppression, renal replacement therapy. CKD without anemia-inclusion criteria: over 18 years, no anemia or treatment for anemia, CKD with stable creatinine values three months before enrollment. Exclusion criteria: medical conditions known to have a role in the development of polycythemia. Hepcidin-25 and ferritin were measured by ELISA method. Erythropoietin (EPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6 were evaluated using chemiluminescent enzyme immunometric assays. Unpaired T test, Pearson correlation and multiple regression were used for statistical analysis.
Results: Hemoglobin values were significantly lower in anemia group. There were no differences in terms of eGFR, age, body mass index, serum hepcidin, erythropoietin, fibrinogen, IL-6, and TNF-α between CKD patients with and without anemia. Serum hepcidin correlated positively with ferritin (r=0.45 p<0.05), TNF-α (r=0.54, p<0.05) and negatively with erythropoietin (r=-0.51, p<0.05). Multiple linear regression analysis demonstrated that TNF-α is an independent predictor of serum hepcidin in our patients (p=0.003, R=0.71).
Conclusion: We found no differences in serum hepcidin, erythropoietin and inflammatory markers in non-dialysis CKD patients with and without anemia.

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