Eczacılık Fakültesi / Faculty of Pharmacy

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A Comprehensive Examination of UV-VIS Spectrophotometric Methods in Pharmaceutical Analysis Between 2015-2023
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-06) Enes, Duygu; Dastan, Kerem; Kaplan, Ozan; Celebier, Mustafa; Dogan, Aysegul
Background: Quality control is a system of validated procedures in which many samples, including active pharmaceutical ingredients and final products, are analyzed using standard or validated analytical methods. Method: Analytical methods used in analyzing active pharmaceutical ingredients or final products in the pharmaceutical industry can be methods registered in pharmacopeias and developed by the company itself. For this reason, published papers related to pharmaceutical analysis attract analysts and researchers' attention. In this study, pharmaceutical analysis and bioanalysis studies carried out between 2015 and 2023 were examined using Google Scholar, and the recent trends were determined for pharmaceutical analysis. Among the published papers performing conventional analytical techniques for pharmaceutical analysis, those applying UV-VIS spectrophotometry method were selected to predict a future perspective in this study. In addition to the data obtained, the current situation of the pharmaceutical industry was considered to correlate with the obtained data for pharmaceutical analysis. Results: The results were presented with comparative tables and summarizing graphs. Interpreting the results allowed us to determine the trends that pharmaceutical analysis studies will lead in the future. This study can be helpful for researchers working on pharmaceutical analysis in both the industry and academia to predict future trends in pharmaceutical analysis. As a result of the literature research covering the dates 2015-2023, 56% of UV-VIS Spectrophotometric methods are used on pharmaceutical dosage forms, 27% are bulk, 16% are pure, 2% are biological materials, and 0.4% are herbal. Made from materials. Of these studies, 28% were conducted in the 200-240 nm range, 27% were conducted in the 240-300 nm range, and only 44% were conducted at >300 nm. Interpreting the results allowed us to determine the trends that pharmaceutical analysis studies will lead in the future. Conclusion: This study can be helpful for researchers working on pharmaceutical analysis in both the industry and academy side to predict future trends for pharmaceutical analysis.
An Essential Component Of Antimicrobial Stewardship During The COVID-19 Pandemic In The Intensive Care Unit: De-Escalation
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-05-24) Pehlivanli, Aysel; Ozgun, Cigdem; Sasal-Solmaz, Firdevs Gonca; Yuksel, Didem; Basgut, Bilgen; Ozcelikay, Arif Tanju; Unal, Mustafa Necmettin
Background The antimicrobial de-escalation strategy (ADE) plays a crucial role in antimicrobial stewardship, reducing the likelihood of bacterial resistance. This study aims to evaluate how often the intensive care unit (ICU) used ADE for empirical treatment during COVID-19.Materials Adult ICU patients receiving empirical antimicrobial therapy for bacterial infections were retrospectively studied from September 2020 to December 2021. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of the antimicrobial to narrow the antimicrobial spectrum within the first 3 days of therapy, according to the test results and clinical picture.Results A total of 99 patients were included in the study. The number of patients who received empirical combined therapy (38.4%) was lower than those who received monotherapy (61.6%). The most preferred monotherapy (45.9%) was piperacillin-tazobactam, while the most preferred in combination treatment (22.7%) was meropenem. Within the first 3 days of admittance to the ICU, 3% of patients underwent ADE for their empirical antimicrobial therapy, 61.6% underwent no change, and 35.4% underwent change other than ADE. Procalcitonin levels were below 2 mu g/L on the third day of treatment in 69.7% of the patients. Culture or culture-antibiogram results of 50.5% of the patients were obtained within the first 3 days of empirical therapy. There was no growth in the culture results of 21 patients (21.2%) during their ICU stay.Conclusion In this study, ADE practice was much lower than expected. In order to reduce the significant differences between theory and reality, clinical, laboratory, and organisational conditions must be objectively assessed along with patient characteristics.
Determination Of Drug-Related Problems According To Pair Criteria In Dialysis Patients: A Cross-Sectional Study In Tertiary Care Hospital
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-25) Pehlivanli, Aysel; Eren, Sayeste Akkan; Sengul, Sule; Basgut, Bilgen; Erturk, Sehsuvar; Ozcelikay, A. Tanju
Background Dialysis patients are at high risk for drug-related problems (DRPs), which have significant consequences for their morbidity, mortality, and quality of life. Improved clinical outcomes can be achieved by preventing, identifying, and resolving these problems. Methods This is a retrospective observational study. In this study, the PAIR instrument (Pharmacotherapy Assessment in Chronic Renal Disease) was validated for use in Turkish. Validation consisted of three stages: translation back-translation with expert panel evaluation, reliability analysis using the test-retest method, and conceptual validity with both Pharmaceutical Care Network Europe (PCNE) and PAIR used to determine DRPs prevalence. Results In total, 104 patients (mean +/- SD age, 54.1 +/- 15.8 years; 53.8% male) were included in the study. An expert panel evaluated the items in the criterion based on their intelligibility, service of purpose, differentiation, and cultural suitability during the translation stage. Content validity index (CVI) score was found to be 0.95. The reliability analysis was performed by applying the test-retest method and calculating correlation coefficient on 30 randomly selected patients one month later. Correlation coefficient (p) was found to be 0.8. To evaluate conceptual validity, 104 patients' pharmacotherapy plans were assessed using both the PAIR and PCNE criteria. The prevalence of DRPs according to PAIR criteria (100.0%) and PCNE (73.1%) were statistically significantly different (p < 0.001). Conclusions As a result, PAIR criteria can identify clinically relevant DRPs in patients with CKD and is a new, validated tool to be used in Turkey, but may not be adequate for patients receiving dialysis. Therefore, it needs to be reviewed and updated for dialysis patients.
Development And Uv-Vis Spectrophotometric Analysis Of An Ease-Of-Use Pediatric Oral Solution Of Dexamethasone For Personalized Therapies
(JOURNAL OF RESEARCH IN PHARMACY, 2024-10-02) Enes, Duygu; Fidan, Bilge Basak; Kaplan, Ozan; Dogan, Aysegul; Altinoz, Sacide; Celebier, Mustafa; Kaynak, Mustafa Sinan
The usage of dexamethasone for pediatric applications is a well-known issue. In the present study, we developed an oral dexamethasone solution formulation especially aimed for dose-dependent personalized therapies and having excipients known as not harmful to be safely used in pediatrics. The aim of this study was to prepare an easy-of-use pediatric oral solution of dexamethasone and develop an UV/VIS Spectrophotometric method for the evaluation of the stability and quality control of the developed formulation. The primary source of dexamethasone for preparation of the oral pediatric solution was the dexamethasone one-time injectable solutions. This allowed the formulation to be easily prepared in basic laboratory conditions. Dexamethasone content and stability of the formulation were ensured by quantification using the developed UV/VIS Spectrophotometric method validated based on ICH Q2 (R1) guidelines. Simple, fast, reliable, and validated spectrophotometric analysis of dexamethasone was carried out at 269 nm wavelength and the method was linear in a range of 1.00 to 50.00 mu g mL-1.The developed formulation was stable at 4 degrees C at least for three weeks when protected from daylight. The other stability conditions (ambient temperature and -20 degrees C) were also evaluated for the assays. Although the methodology used in this study contains simple processes which can be easily adapted to basic laboratory conditions, the results were satisfactory to prepare an ease-of-use pediatric oral solution of dexamethasonefor personalized medicine. The validated UV/VIS Spectrophotometric method was selective for the formulation and easily applied for the quality control and stability studies of the samples. Such formulations could be helpful for health professionals in managing real-life corticosteroid treatment application problems especially for pediatrics in hospital pharmacy.
Electrospun Hesperidin Nanofibers Induce A Cytoprotective Effect On Sodium-Fluoride Induced Oxidative Stress In Vitro
(JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2024-03-08) Birer, Mehmet; Kara, Adnan Altug; Yurdakok-Dikmen, Begum; Uyar, Recep; Aralan, Gizem; Birer, Yagmur Turgut; Filazi, Ayhan; Acartuerk, Fusun
As a bioactive flavonoid in Citrus seeds, hesperidin exerts significant antioxidant, free radical scavenging, and anticancer activity with limited bioavailability. To enhance the stability and improve the bioactive potential of hesperidin, an electrospun nanofiber formulation was developed. Electrospinning solution was characterized by surface tension, viscosity, and conductivity measurements, and these values were found to be 25.18 +/- 0.04 mN/ m 145 +/- 2 cPs and 9.0 +/- 0.4 mu S/cm, respectively. Electrospun hesperidin nanofiber was tested in a coincubation with the cytotoxic agent sodium fluoride (NaF) in Caco-2 cells. Inhibitory concentration-50 (IC50) values of hesperidin nanofiber in Caco-2 cells alone were as low as 30 mu M, indicating its potential anticancer effect, while coincubation with 10 and 20 mu M of hesperidin nanofibers was found to alleviate the cytotoxic effect induced by NaF at 2.1, 1.05 and 0.525 mM concentrations. This effect was in accordance with cellular antioxidant mechanisms; where malondialdehyde (MDA) levels at 10 mu M hesperidin nanofiber were found to be decreased by 55.60% in the thiobarbituric acid reactive substances (TBARS) assay, and the mRNA expression of Thioredoxin1 (TRX1) and Superoxide dismutase-1 (SOD1) were decreased in qPCR. The results revealed that electrospun nanofiber of hesperidin was developed for the first time with useful implications against cellular toxicity by alleviating the cellular antioxidant defense mechanisms, including MDA, SOD1, and TRX1.
Green Hplc Method For Simultaneous Determination Of N-Acetylcysteine And L-Ascorbic Acid In Co-Formulated Pharmaceutical Products
(JOURNAL OF RESEARCH IN PHARMACY, 2024-10-02) Ozen, Gurkan; Nemutlu, Emirhan
It is difficult to analyze different concentrations of pharmaceutical active substances in dosage forms simultaneously, especially in formulations containing high amounts of excipients, on environmentally friendly principles without the need for any intervention. This study proposes a powerful analytical method for the simultaneous determination of L-ascorbic Acid and N- Acetyl Cysteine in an effervescent tablet using high performance liquid chromatography technique. In the study, it was aimed to reduce the use of toxic solvents/chemicals and waste emissions, to increase efficiency and to reduce the negative environmental consequences that may arise from them. The method was developed using a C18 (ACE-121-2546, 4.6 x 250 mm, 5 mu m) column and a sodium dihydrogen phosphate buffer mobile phase. Detection wavelengths were taken as 210 and 240 nm while the flow rate was 1 mL/min. The linearity, accuracy and precision, selectivity, sensitivity, and robustness of the proposed method were validated using International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Q2R criteria and its green assessment was validated by AGREE and AGREEprep applications. The linear range was taken as 0.1-100 mu g/mL for both compounds analyzed in the developed method. The detection limit of the method was 0.02 and 0.04 mu g/mL respectively for L-ascorbic Acid and N- Acetyl Cysteine. The recovery of the method was between 98.75%102.20% and the accuracy and precision of the method for all compounds were 0.17% and 0.11% respectively. This new environmentally friendly method can be easily used by the chemical and pharmaceutical industries for regular analysis without any restrictions.
New Ester-Containing Azole Derivatives With Potent Anti-Candida Effects: Synthesis, Antifungal Susceptibility, Cytotoxicity, and Molecular Modeling Studies
(DRUG DEVELOPMENT RESEARCH, 2024-11) Ataker, Yusuf; Oncue, Ozge; Gulmez, Dolunay; Sabuncuoglu, Suna; Arikan-Akdagli, Sevtap; Sari, Suat
Mortalities due to mycoses have dramatically increased with the emergence of drug-resistant strains and growing immune-compromised populations globally. Azole antifungals have been the first choice against fungal infections of a wide spectrum and several azole derivatives with ester function were reported for their potentially promising and favorable activity against Candida spp. In this study, we designed and synthesized a series of 1-(aryl)-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1-yl)ethyl esters, and tested them against seven reference Candida strains using EUCAST reference microdilution method. Among the series, 6a, 6d, and 6g proved highly potent in vitro compared to fluconazole; especially against Candida albicans and Candida tropicalis with minimum inhibitor concentration (MIC) values as low as 0.125 and 0.06 mg/L, respectively, although their activities against Candida krusei and Candida glabrata remained limited. The compounds also showed minimal toxicity to murine fibroblasts according to the in vitro cytotoxicity tests. Molecular modeling predicted 6g as an orally available druglike compound according to all parameters and CYP51 inhibition as the likely mechanism for their antifungal effects. The study underpins the promise of azoles with ester functionality as a potential scaffold for small-molecule antifungal drug design.
Pharmacy Practice And Policy Research In Türkiye: A Systematic Review Of Literature
(JOURNAL OF PHARMACEUTICAL POLICY AND PRACTICE, 2024-12-31) Gulpinar, Gizem; Pehlivanli, Aysel; Babaar, Zaheer Ud-Din
BackgroundIn recent decades, there has been an interest in clinical pharmacy practice in T & uuml;rkiye with emerging studies in this area. Despite the recent emergence of diverse pharmacy practice studies in T & uuml;rkiye, a comprehensive assessment of overall typology of studies and impact has not been conducted thus far.ObjectivesThis systematic review aims to document and assess pharmaceutical policy and practice literature published within the last 5 years in T & uuml;rkiye. The other aim is to summarise the expected impact of published studies on policy and practice research.MethodsThe systematic review was conducted according to the guidelines described in the PRISMA Statement. A comprehensive search approach, incorporating Medical Subject Headings (MeSH) queries and free-text terms was employed to locate pertinent literature related to pharmacy practice and policy in T & uuml;rkiye. The search covered the period from January 1, 2019, to January 1, 2024, and involved electronic databases including PubMed, Medline Ovid, Scopus, ScienceDirect, Springer Link, PlosOne, and BMC.ResultsIn the final grouping, 73 articles met the inclusion criteria and were selected for this review. Among the quantitative studies, majority studies were cross-sectional survey studies. Through the rigorous thematic content analysis seven research domains were developed from the selected literature: drug utilisation and rational drug use, the emerging role of pharmacist, access to medicines and generic medicines, community pharmacy practice, pharmacovigilance/adverse drug reactions, and pharmacoeconomic studies.ConclusionsThe pharmacist role is evolving; however, several challenges remain in fully realising the potential of pharmacists. These include regulatory barriers, limited public awareness of pharmacists' expanded roles, workforce capacity issues, and the need for ongoing professional development and training. Research studies are needed in the areas of generic prescribing, medicine adherence, intervention studies in community and hospital pharmacy practice, and on pharmacoeconomics and pharmacovigilance.
Potent Antimicrobial Azoles: Synthesis, In Vitro and In Silico Study
(ANTIBIOTICS-BASEL, 2024-11) Ozdemir, Zeynep; Zenni, Yaren Nur; Karakurt, Arzu; Sari, Suat; Sarac, Selma; Akdag, Mevluet; Merde, Irem Bozbey; Kart, Didem; Venanzoni, Roberto; Flores, Giancarlo Angeles; Angelini, Paola; Kabier, Muzammil; Mathew, Bijo; Carradori, Simone
Background/Objectives: The increase in fungal infections, both systemic and invasive, is a major source of morbidity and mortality, particularly among immunocompromised people such as cancer patients and organ transplant recipients. Because of their strong therapeutic activity and excellent safety profiles, azole antifungals are currently the most extensively used systemic antifungal drugs. Antibacterial properties of various topical antifungals, such as oxiconazole, which features oxime ether functionality, were discovered, indicating an exciting prospect in antimicrobial chemotherapy. Methods: In this study, eleven new oxime ether derivatives with the azole scaffold (5a-k) were synthesized and tested for their antimicrobial effects using the microdilution method to obtain broad-spectrum hits. Results: Although the title compounds showed limited efficacy against Candida species, they proved highly effective against dermatophytes. Compounds 5c and 5h were the most potent derivatives against Trichophyton mentagrophytes and Arthroderma quadrifidum, with minimum inhibitory concentration (MIC) values lower than those of the reference drug, griseofulvin. The MIC of 5c and 5h were 0.491 mu g/mL and 0.619 mu g/mL against T. mentagrophytes (MIC of griseofulvin: 2.52 mu g/mL). The compounds were also tested against Gram-positive and Gram-negative bacteria. Briefly, 5c was the most active against Escherichia coli and Bacillus subtilis, with MIC values much better than that of ciprofloxacin (MIC of 5c = 1.56 mu g/mL and 1.23 mu g/mL, MIC of ciprofloxacin = 31.49 and 125.99 mu g/mL, respectively). Molecular docking suggested a good fit in the active site of fungal lanosterol 14 alpha-demethylase (CYP51) and bacterial FtsZ (Filamenting temperature-sensitive mutant Z) protein. Conclusions: As a result, the title compounds emerged as promising entities with broad antifungal and antibacterial effects, highlighting the utility of oxime ether function in the azole scaffold.
The Clinical Efficacy of Adding Ceftazidime/Avibactam to Standard Therapy in Treating Infections Caused by Carbapenem-Resistant Klebsiella pneumonia with blaOXA-48-like Genes
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-03) Jaber, Al Maamon R. Abu; Basgut, Bilgen; Hawan, Ali Abdullah; Al Shehri, Ali Amer; AlKahtani, Sultan Ahmad; Ahmed, Nehad J.; Abdi, Abdikarim
Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.
The Impact of Clinical Pharmacist in Geriatric Drug-Related Problems: A Scoping Review
(Başkent Üniversitesi, 2024-02-01) Ediz, Cigdem; Bicer, Asim Emre; Pehlivanli, Aysel; Basgut, Bilgen; Ozcelikay, Arif Tanju