Turkish Journal of Pharmaceutical Sciences最新文献

Objectives: The lack of a specific proven treatment for coronavirus disease-2019 (COVID-19) has led individuals to use different treatment options. Although their effects on COVID-19 have not been proven, interest in dietary supplements and aromatherapy has increased during the pandemic period. In this study, use of dietary supplements and aromatherapy was investigated for COVID-19 among individuals living within the borders of Türkiye.

Materials and methods: This cross-sectional survey study was conducted among 310 individuals. The questionnaire was prepared using online Google Forms and communicated to the participants via social media platforms. The data obtained from the study were analyzed with the statistical program.

Results: The analyzes of the survey revealed that participants increased the usage of supplements mostly prophylactic and for treatment purposes during COVID-19 pandemic, 31.9% individuals declared that they consumed herbal tea/products, 38.1% of them used vitamin/mineral supplements (multivitamin-mineral, vitamins B1, B6, B12, C, D, calcium, coenzyme Q10, iron, magnesium, selenium, and zinc), and 18.4% of the individuals applied aromatherapy (meaning treatment with essential oils). As a result of the study, the most commonly used supplement was vitamin D, the most commonly consumed tea was green tea, the essential oil was thyme oil, and the most eaten vegetable was garlic. Moreover, other frequently used herbal products were found to contain ginger and onion as food and peppermint and eucalyptus oils as aromatherapeutics. Participants often reported that they found it safe to use elevated levels of herbs or herbal products against COVID-19.

Conclusion: Among the individuals participating in this study, it has been observed that the use of dietary supplements has increased during the COVID-19 pandemic period. The study revealed that vitamin D is prominent in self-medication use. Moreover, interest in aromatherapy and dietary supplements has increased. Among aromatherapeutics, thyme stood out over the applied essential oils.

Objectives: Trachystemon orientalis (L.) G. Don, colloquially known in Türkiye as "kaldırık", is an edible plant belonging to the Boraginaceae. This plant has been practiced in traditional medicine for many years for its various therapeutic benefits. The effectiveness and chemical composition of plants can vary depending on their parts, age, and extraction solvent. Therefore, the current study aimed to define the biological activities of various parts and extracts of T. orientalis, which were collected in distinct seasons as young and mature, and investigate the main component responsible for these biological effects.

Material and methods: Plant material was collected in different seasons from the northwest of Türkiye. 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activities were investigated to assess antiradical and antioxidant potential of the extracts. Anti-inflammatory activity of the extracts was also tested using human red blood cell membrane stabilizing method. Folin-Ciocalteu test was conducted to determine the total phenolic content. Reverse phase-high performance liquid chromatography-photodiode array detector (RP-HPLC-PDA) analysis was performed.

Results: Both methanol and aqueous extracts exhibited significant radical scavenging and anti-inflammatory activities compared with control (p<0.05). The highest percentage of inhibition on ABTS and DPPH free radicals was obtained in aqueous extracts of the mature herbs and roots, respectively. Methanol extracts of the mature roots and herbs exhibited the strongest anti-inflammatory capacity. Rosmarinic acid possessed a much higher antioxidant and anti-inflammatory effect than the reference compounds used in each assay in our study. High rosmarinic acid content of the extracts suggests that the compound responsible for the great biological activity potential is rosmarinic acid.

Conclusion: To the best of our knowledge, the presence of rosmarinic acid in herbs and roots of T. orientalis was shown for the first time in our present study. Phytochemical composition and effective biological activities of T. orientalis explain its traditional use and indicate its significant potential in pharmaceutical industry applications.

Objectives: Xanthohumol (XH) is a prenylated chalcone available naturally and has diverse pharmacological activities. It has some limitations in the physiological environment such as biotransformation and less gastrointestinal tract absorption. To overcome the limitations, we prepared nanoformulations [solid lipid nanoparticles (SLNs)] of XH. Therefore, an analytical method is required for the estimation of XH in the bulk nanoformulations, so we developed and validated a quality by design (QbD)-based ultraviolet (UV)-spectrophotometric method as per the International Conference of Harmonization (ICH) Q2 (R1) guidelines.

Materials and methods: The new analytical Qbd based UV-visible spectrophotometric technique is developed and validated for estimation of XH in bulk and SLNs as per ICH guidelines Q2 (R1). Critical method variables are selected on the basis of risk assessment studies. Optimization of method variables was performed using the a central composite design (CCD) model.

Results: Multiregression ANOVA analysis showed an R2 value of 0.8698, which is nearer to 1, indicating that the model was best fitted. The optimized method by CCD was validated for its linearity, precision, accuracy, repeatability, limit of detection (LOD), limit of quantification (LOQ), and specificity. All validated parameters were found to be within the acceptable limits [% relative standard deviation (RSD) <2]. The method was linear between 2-12 g/mL concentration with R2 value 0.9981. Method was accurate with percent recovery 99.3-100.1%. LOD and LOQ were found to be 0.77 and 2.36 μg/mL, respectively. The precision investigation confirmed that the method was precise with %RSD <2.

Conclusion: The developed and validated method was applied to estimate XH in bulk and SLNs. The developed method was specific to XH, which was confined by the specificity study.

Objectives: Breast cancer is the most frequently diagnosed cancer type and the second leading cause of cancer-related death in women. Recent studies have highlighted the importance of the endoplasmic reticulum (ER) protein quality control mechanism for the survival of many cancers. It has also been recommended as a good target for the treatment of many cancer types. Homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1) functions as one of the main components of ER-associated degradation, which is an ER-resident protein quality mechanism. Today, the association of HERPUD1 with breast carcinogenesis is still not fully understood. Herein, we evaluated the possibility of HERPUD1 as a potential therapeutic target for breast cancer.

Materials and methods: The effects of HERPUD1 silencing on epithelial-mesenchymal transition (EMT), angiogenesis, and cell cycle proteins were analyzed by immunoblotting studies. To test the role of HERPUD1 on tumorigenic features, WST-1-based cell proliferation assay, wound-healing assay, 2D colony formation assay, and Boyden-Chamber invasion assay were performed in human breast cancer cell line MCF-7. The statistical significance of the differences between the groups was determined by Student's t-test.

Results: Our results displayed that suppressing HERPUD1 expression reduced the cell cycle-related protein levels, including cyclin A2, cyclin B1, and cyclin E1 in MCF-7 cells. Also, silencing of HERPUD1 remarkably decreased expression levels of EMT-related N-cadherin and angiogenesis marker vascular endothelial growth factor A. Moreover, we determined that cell proliferation, migration, invasion, and colony formation of MCF-7 cells were significantly limited by silencing of HERPUD1.

Conclusion: Present data suggest that HERPUD1 may be an effective target for biotechnological and pharmacological strategies to be developed to treat breast cancer.

Adverse drug reactions (ADRs) are a prominent cause of morbidity and mortality and higher healthcare expenditures. Healthcare professionals (HCPs) play a crucial role in ADR reporting through spontaneous reporting systems, but under-reporting is their major limitation. The goal of this study is to evaluate HCPs' knowledge, attitude, and practice regarding ADR reporting as well as the factors that influence reporting using research papers that are currently available. A literature search was conducted using sources such as PubMed, Scopus, and Google Scholar to find studies that evaluated HCPs' knowledge, attitudes, and practices regarding ADRs reporting in Ethiopia. A standard procedure of systematic review protocol was used to conduct this review. Demographic factors, sample size, response rate, survey delivery, HCP working setting, and encouraging and discouraging factors of ADR reporting were extracted from articles. A total of 17 articles were included in the systematic review out of 384. The number of HCPs in the included studies ranged from 62 to 708. Response rate ranges from 76.1% to 100%. Most of the research included in this evaluation looked at HCPs, who worked in hospitals. When pharmacists were compared to other HCPs, they were more likely to report ADRs; because they had higher knowledge, attitude, and practice. Lack of understanding, unavailability of reporting forms, uncertainty about the causal relationship between the drug and ADR, and failure to report because the ADR was well known were among the common hurdles to ADR reporting identified in research. To improve reporting, educational initiatives and continued training in pharmacovigilance and ADRs are frequently recommended considerations. In Ethiopia, there is a pressing need to close the gap in HCP knowledge, attitudes, and practice regarding PV and ADR reporting. To address this point, specific educational interventions based on existing gaps in ADR reporting should be developed and integrated into the health education curriculum or provided as in-service training after graduation.

Objectives: This study constructed dorzolamide (DRZ)-loaded ophthalmic implants for extended drug delivery and increased drug retention.

Materials and methods: Carboxymethyl cellulose (CMC) and chitosan (CHI) were used to describe the ophthalmic implants. The implants were prepared by the solvent casting technique in presence of polyethylene glycol 6000 (PEG 6000) as plasticizer. Physicochemical characterization studies including mechanical characteristics [tensile strength (TS), elongation at break, and Young's modulus], bioadhesion studies, and in vitro and ex vivo drug release studies were conducted.

Results: TS of drug-loaded ophthalmic implants was 10.70 and 11.68 MPa, respectively. Elongation at break of CMC and CHI implants was 62.00% and 59.05%, respectively. The in vitro release profiles fit into Higuchi type kinetic model. Ex vivo release study results for both implants were correlated with in vitro release investigations.

Conclusion: CMC and CHI-based implants provide extended drug delivery. Implants prepared using CMC provided a significantly slower in vitro release rate, and drug retention on ocular surfaces increased. Thus, it has been concluded that DRZ-loaded CMC implants could provide effective treatment for glaucoma.

Objectives: Dexketoprofen is a non-steroidal analgesic/anti-inflammatory drug and its trometamol salt is extensively preferred in mild or moderate pain due to its rapid onset of relief. A new formulation of 36.9 mg of dexketoprofen trometamol (equivalent to 25 mg dexketoprofen) tablet has been developed and its bioequivalence to the reference product was proven.

Materials and methods: An open-label, single-dose, randomized, two-period, and cross-over bioequivalence study was conducted with healthy males under fasting conditions for two different tablet formulations of 25 mg dexketoprofen. To prove the bioequivalence of the test product with the reference product, a comparison study has been performed in compliance with regulations in force under Good Clinical Practice principles. A single-center clinical study was run and blood samples of the participants were withdrawn at specified time points, before and after dosing, to measure the plasma concentrations of dexketoprofen trometamol. A validated analytical method has been developed using an liquid chromatography with tandem mass spectrometry. Instrument to assess the plasma concentrations of the test and reference products.

Results: Forty-seven volunteers completed clinical phase of the study. For the test and reference products, the mean ± standard deviations (SD) of C_max were found 2543.82 ± 655.42 ng/mL and 2539.11 ± 662.57 ng/mL, and the mean ± SD of area under the curve (AUC) from time 0 to the last measurable concentration (AUC_0-tlast) were found 3483.49 ± 574.42 h.ng/mL and 3560.75 ± 661.83 h.ng/mL, respectively. The primary target variables data demonstrate the bioequivalence of test and reference products with regard to 90% confidence interval for C_max of 92.45-108.53% and for AUC_0-tlast of 95.57-100.87%. The geometric mean ratios were found as 100.16% and 98.18% for C_max and AUC_0-tlast, respectively. There were no serious adverse events or adverse reactions reported throughout the study.

Conclusion: After statistical evaluation of the analytical results, the test and reference products were considered bioequivalent. Both products were well tolerated and considered as safe.

Objectives: Rutin has been broadly applied for treating several diseases due to its pharmacological activities. However, its low aqueous solubility limits its absorption and bioavailability. This research aims to increase the solubility of rutin using cyclodextrin and to develop a temperature-triggered in situ gelling system for dermal application.

Materials and methods: The solubility of rutin was increased with sulfobutyl ether-β-cyclodextrin (SBE-β-CD). Rutin- SBE-β-CD inclusion complex was prepared by kneading and freeze dying method. Structural characterization was carried out using differential scanning calorimetry and fourier transform infrared spectroscopy. In situ gel formulations were prepared with pluronic F127 (PF127), a thermosensitive polymer, and chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer. In situ gel characteristics such as pH, clarity, gelation temperature, and viscosity were determined.

Results: When the solubility diagrams were examined, it was concluded that SBE-β-CD showed a linear increase, therefore, AL-type diagram was selected. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. Three in situ gels were evaluated for their pH, gelling temperature, and the rheological behaviors, and one formulation was selected. It was observed that the formulations had a pH between 6-6.1, and their gelation temperature decreased with increasing PF127 that was between 20°C to 34°C. For the selected formulation (formulation E3), 0.5% rutin and rutin/SBE-β-CD were transferred to the in situ gelling system. Because of in vitro release studies, it was observed that the release of the rutin/SBE-β-CD inclusion complex containing NZ formulation showed a higher burst effect than the others and the release continued for 6 hours.

Conclusion: The results indicated that the combination of PF127 and CH can be a hopeful in situ gelling vehicle for dermal delivery of rutin and rutin/SBE-β-CD.

Objectives: Mefenamic acid (MA) is a strong non-steroidal anti-inflammatory drug, but because of its limited oral bioavailability and the side effects that come with taking it systemically, it is better to apply it topically. The major goal of this study was to see how certain permeation enhancers affected MA is in vitro skin permeability. In manufactured Franz diffusion cells, MA permeability tests using rat skin pretreatment with several permeation enhancers such as corn oil, olive oil, clove oil, eucalyptus oil, and menthol were conducted and compared to hydrate rat skin as a control.

Materials and methods: The steady-state flux (Jss), permeability coefficient (Kp), and diffusion coefficient are among the permeability metrics studied. The permeability enhancement mechanisms of the penetration enhancer were investigated using fourier transform infrared spectroscopy (FTIR) to compare changes in peak position and intensities of asymmetric and symmetric C-H stretching, C=O stretching, C=O stretching (amide I), and C-N stretching of keratin (amide II) absorbance, as well as differential scanning calorimetry (DSC) to compare mean transition temperature and their enthalpies.

Results: Clove oil, olive oil, and eucalyptus oil were the most effective enhancers, increasing flux by 7.91, 3.32, and 2.6 times, as well as diffusion coefficient by 3.25, 1.34, and 1.25, respectively, when compared to moist skin. FTIR and DSC data show that permeation enhancers caused lipid fluidization, extraction, disruption of lipid structures in the SC layer of skin, and long-term dehydration of proteins in this area of the skin.

Conclusion: According to the findings, the permeation enhancers used improved drug permeability through excised rat skin. The most plausible mechanisms for greater ERflux, ERD, and ERP ratios were lipid fluidization, disruption of the lipid structure, and intracellular keratin irreversible denaturation in the SC by eucalyptus oil, menthol, corn oil, olive oil, and clove oil.