Turkish journal of pharmaceutical sciences最新文献

Objectives: The objective of this study was to develop a simple, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method for the simultaneous estimation of dapagliflozin (DAP) and vildagliptin (VIL) in a combined pharmaceutical formulation. Managing diabetes often involves using a combination of drugs to better control blood sugar levels. One such effective formulation is combination of DAP, an SGLT2 inhibitor, with VIL, a DPP-4 inhibitor, in a single formulation. To ensure the quality and consistency of these combination products, it is important to have a simple and reliable method for analyzing both drugs simultaneously.

Materials and methods: An aluminium-backed pre-coated silica gel 60 F₂₅₄ TLC plate was employed as the stationary phase. The mobile phase consisted of toluene, methanol, and ethyl acetate in a volumetric ratio of 5:3:2. Prior to plate development, the chamber was saturated with the mobile phase for 20 minutes. Detection was carried out at 210 nm, selected based on the isosbestic point of the analytes.

Results: The developed method successfully separated the analytes with retardation factor values of 0.57±0.02 for DAP and 0.26±0.02 for VIL. The method exhibited linearity in the concentration ranges of 0.6 to 1.4 μg per band for DAP, with a correlation coefficient (r²) of 0.997 and 6 to 14 μg per band for VIL, with an r² of 0.998. The limit of detection was found to be 0.02 μg/band for DAP and 0.19 μg/band for VIL. Similarly, the limit of quantification was determined to be 0.07 μg/band for DAP and 0.58 μg/band for VIL.

Conclusion: The proposed HPTLC method allows for the simultaneous estimation of DAP and VIL with high accuracy, precision, and sensitivity. Owing to its satisfactory analytical performance, the method is suitable for routine quality control of combined dosage forms containing DAP and VIL.

Objectives: Comprehensive Medication Management (CMM) is pivotal in optimizing clinical outcomes through personalized medication review and patient engagement. Patient satisfaction surveys, such as the Medication Management Patient Satisfaction Survey (MMPSS), play a crucial role in assessing the quality of these services. However, there is currently no Turkish version of the MMPSS available. This study aimed to translate, culturally adapt, and validate the Turkish version of the MMPSS to assess patient satisfaction with CMM services provided by pharmacists in Türkiye.

Materials and methods: Following established guidelines for cross-cultural instrument validation, the MMPSS was translated into Turkish and culturally adapted. The survey underwent forward translation, expert panel review, back-translation, and pilot testing. Data collection occurred in a tertiary care university hospital between September 9, 2022, and March 21, 2023. Psychometric analyses included reliability testing (Cronbach's alpha), factorial validity using confirmatory factor analysis, and test-retest reliability using the Intraclass Correlation Coefficient (ICC).

Results: A total of 124 participants (82.7%) completed the survey. Participants were mostly women (57.3%) and elderly, with a mean age of 70.43 years, three comorbidities, and six medications. The Turkish MMPSS demonstrated excellent internal consistency (Cronbach's α = 0.858) and test-retest reliability (ICC=0.937), confirming its reliability over time. Factor analysis supported a one-factor structure, consistent with the original MMPSS framework, and all items showed strong correlations.

Conclusion: The Turkish version of the MMPSS is a reliable and valid instrument for assessing patient satisfaction with CMM services in Türkiye. Its implementation can enhance the evaluation and improvement of clinical pharmacy services, ultimately promoting better patient care and outcomes.

Objectives: Pharmacoeconomics is an important branch of science that should be taken into account by countries' social security institutions in order to rationally manage drug expenditures within healthcare budgets for the aging population. Pharmacists trained in pharmacoeconomics make a great contribution to this field. This study aims to draw attention to the inclusion of pharmacoeconomics education as a compulsory course in the curricula of pharmacy faculties in Türkiye.

Materials and methods: Fifty-one pharmacy faculties in Türkiye were analysed. The pharmacoeconomics courses and their contents in the curriculum of these faculties were evaluated. The course contents, European Credit Transfer System and credits, weekly and meeting hours of the faculties offering pharmacoeconomics courses were analyzed.

Results: There are 51 pharmacy faculties in Türkiye. Of these pharmacy faculties, 33 are operating under state universities and 18 under foundation universities. There is no pharmacoeconomics course in the curriculum of 82.35% of the pharmacy faculties (n=42). In the other 17.65% (n=9) of the faculties, there is a pharmacoeconomics course in the curriculum. The course contents of the faculties are similar, and basic pharmacoeconomics information is generally given. There are no faculty members who have completed their PhDs in this field.

Conclusion: This study, the first to systematically evaluate the situation in all pharmacy faculties in Türkiye, has revealed that pharmacoeconomics education is limited. Making pharmacoeconomics courses mandatory in the curriculum of pharmacy faculties is necessary to comply with international standards and enable pharmacists to contribute more effectively to rational drug use and the sustainability of healthcare systems.

Objectives: Antimicrobial resistance is a major problem in the treatment of infectious diseases. Therefore, it is important to develop new and effective antimicrobial agents. For this purpose, a new series of compounds with a 2,4-dihydro-3H-1,2,4-triazole-3-thione structure was synthesized.

Materials and methods: 2,4-dihydro-3H-1,2,4-triazole-3-thione compounds (T1-T8) were synthesized by heating thiosemicarbazide derivatives under alkaline conditions. Infrared (IR), ¹H-NMR, and ¹³C-NMR spectroscopic methods were used to elucidate the chemical structures of the compounds. The antimicrobial activity of the compounds against eight bacterial strains (five Gram-negative and three Gram-positive) and two fungal strains was evaluated using the microdilution method.

Results: Compounds T4, carrying a benzoyl group, and T6, carrying a phenethyl group, showed the best antibacterial activity against Enterococcus faecalis ATCC 29212, with minimum inhibitory concentrations (MICs) of 41.79 mg/L and 81.25 mg/L, respectively. Compound T6 also demonstrated the strongest antibacterial activity against Staphylococcus epidermidis ATCC 12228, with an MIC of 40.62 mg/L. Antifungal activity assays revealed that compounds T4, T6, and T8 were the most potent against Candida albicans ATCC 90028, with MIC values of 40.62-83.59 mg/L, and that T6, T7, and T8 were the most potent against Candida glabrata ATCC 90030, with MIC values of 40.62-162.5 mg/L.

Conclusion: Among the compounds, T6 appears to exhibit significant antimicrobial activity against both Gram-positive bacteria (e.g., E. faecalis ATCC 29212 and S. epidermidis ATCC 12228) and fungi (e.g., Candida strains).

Objectives: Comorbid psychiatric disorders, especially depression, pose challenges in epilepsy. Antiepileptic drugs, including levetiracetam, can also have psychiatric adverse effects, necessitating strategies to address mood regulation. The study aims to assess the impact of melatonin administration on depressive behavior in epileptic and non-epileptic mice.

Materials and methods: Male albino mice were assigned to different treatment groups. Levetiracetam (20 mg/kg ip) was injected for 14 days; melatonin (25 mg/kg ip) was injected for 7 days. Additional groups were included for epileptic mice. Maximal electroshock was used to induce seizures: locomotor activity, immobility time in the forced swimming test (FST), latency, and food consumption were measured in the novelty-suppressed feeding test (NSFT).

Results: There were insignificant differences in locomotor activity between groups. In the FST, levetiracetam administration significantly increased the immobility duration compared to the control group in epileptic and non-epileptic mice (p<0.05). The immobility duration in the levetiracetammelatonin groups of both epileptic and non-epileptic mice significantly decreased compared to the levetiracetam alone group (p<0.01). In NSFT, the levetiracetam group exhibited a significantly longer latency (p<0.01) and less food intake (p<0.05) compared to the control group; these changes were reversed when levetiracetam-melatonin was administered. In epileptic groups, the difference in latency was insignificant, while food consumption increased significantly (p<0.05) in the levetiracetam-melatonin group compared to the levetiracetam-alone group. The results observed with melatonin were similar to those of imipramine.

Conclusion: Melatonin was found to reduce depressive behavior in both non-epileptic and epileptic groups. These results suggest that melatonin could be a potential therapeutic agent for countering the depressive effects of levetiracetam.

Objectives: This study aims to enhance the bioavailability and polymorphic stability of Ticagrelor, a metastable, low-soluble and low-permeable Biopharmaceutics Classification System Class IV drug, by exploring different formulation approaches.

Materials and methods: Ticagrelor was taken as a model drug for the enhancement of bioavailability and polymorphic stability. Initially, various techniques, such as micronization, amorphous solid dispersion (ASD), and Self-Microemulsifying Drug Delivery System, were evaluated for dissolution enhancement. Based on the improvement in dissolution rate, polymorphic stability, and process viability, an ASD technique was selected for dissolution enhancement of Ticagrelor. Co-povidone VA 64 and vitamin E TPGS were used as carriers for the preparation of Ticagrelor solid dispersion (SD) by the solvent evaporation technique. The formulation was optimized and further evaluated for dissolution performance in biorelevant media fasted state simulated gastric fluid and fasted state simulated intestinal fluid. The bioavailability of the Ticagrelor SD tablet formulation was compared with a conventional immediate release tablet formulation prepared by wet granulation process in line with reference product Brilinta^® (AstraZeneca LP). In vivo pharmacokinetic (PK) studies were carried out in Wistar rats with due approval from ethics committees such as CPCSEA and IAEC (CPCSEA/DIPS/02/23/61). Patients are not involved in this study, hence informed consent not applicable.

Results: The relative bioavailability and peak plasma concentration (C_max) of Ticagrelor SD formulation compared to conventional immediate release tablet formulation in line with Brilinta^® (AstraZeneca LP) were found to be 141.61±2.29% and 137.0±0.59%, respectively. Further, based on a doseadjusted PKs study of Ticagrelor SD, a 70 mg Ticagrelor tablet formulated with the SD technique was found to be equivalent to a 90 mg dose of Ticagrelor conventional immediate release tablet formulation with a comparable C_max, area under the curve (AUC)_0-24, and AUC_0-∞. Visual observation of the dissected gastric organ through a stereomicroscope revealed no redness or bleeding post-administration of Ticagrelor SD formulations.

Conclusion: The SD technique with carrier co-povidone VA 64 and vitamin E TPGS prepared by the solvent evaporation process could yield a Ticagrelor formulation with improved bioavailability and polymorphic stability.

Objectives: This study aimed to incorporate a pharmacy management course into pharmacy education and explore students' time management and career planning attitudes in relation to this course.

Materials and methods: This research, conducted between October 2, 2023, and January 12, 2024, employed a mixed-methods design, integrating both qualitative and quantitative research methodologies within a single study framework. Quantitative data were collected using the Sociodemographic Form, Career Futures Inventory (CFI), and Time Management Questionnaire (TMQ). A semi-structured interview form was employed to gather qualitative data. This study included 60 fifth-year pharmacy students. The experimental group (n=30) comprised volunteers enrolled in the "Management in Pharmacy" elective course, while the control group (n=30) consisted of randomly selected volunteers not enrolled in the course.

Results: In the intervention group, pre-test TMQ scores ranged from 56 to 117, yielding a mean score of 80.50±16.12. Post-test scores ranged from 55 to 112, with an average of 86.83±14.09. There was a significant difference in the change in the TMQ scores and Time Attitude scores between the control and intervention groups (p=0.003 and p=0.001, respectively). For the intervention group, pre-test CFI scores ranged from 63 to 116, yielding a mean score of 85.93±15.34. Post-test scores ranged from 68 to 111, with an average of 89.40±12.56. No significant difference was observed in the change in the CFI scores between the control and intervention groups (p=0.311). Student feedback provided insight into the necessity or usefulness, impact, and future suggestions concerning the delivery of this course.

Conclusion: The implementation of educational resources and methodologies aimed at fostering time management abilities and encouraging career planning attitudes from the initial phases of pharmacy education may result in greater outcomes.

Objectives: Lycopene is a powerful antioxidant with diverse health benefits. However, it belongs to the Biopharmaceutics Classification System II; thus, it depicts poor water solubility and dissolution. Its lipophilic nature hinders the bioavailability of this drug. To overcome these limitations, namely, poor solubility and bioavailability, several approaches have been tried so far, such as co-solvency, size reduction or micronization, complexation, adsorption on high surface area carriers, etc. The present research aimed to apply the liquisolid technique to prepare lycopene liquisolid compacts with an improved dissolution profile. The impact of parameters such as carrier and drug concentration percentage on drug dissolution was evaluated in liquisolid compacts.

Materials and methods: Lycopene was extracted by Soxhlet extractionand then characterized by ultraviolet spectroscopy, infrared spectroscopy, thin-layer chromatography, and melting point. Liquisolid compacts of lycopene were formulated by using excipients such as non-volatile solvent (glycerine), carrier (Avicel PH 101, Fujicalin, Neusilin US2), disintegrant (Croscarmellose sodium), and diluent (lactose). The different formulation batches of liquisolid compacts were formulated and evaluated based on different pre-compression and post-compression parameters.

Results: Powder X-ray Diffraction (PXRD) and Fourier transform infrared spectroscopy were utilized to analyze drug-excipient interaction; these studies showed no evidence of any physical or chemical interaction between the drug(s) and the excipients. The PXRD of lycopene showed sharp and intense peaks at diffraction angles (2θ) such as 12.563, 19.176, 19.636, 20.062, 21.283, 26.629, 29.479, 30.235, and 39.997, which indicates a crystallinestructure. The PXRD of the physical mixture of lycopene and excipients showed similar sharp peaks (12.582, 19.202, 19.634, 20.045, 21.304, 26.565, 29.474, 30.250, and 40.065), indicating thatthere is no drug-excipient interaction occurring. Lycopene was extracted and characterized. IR spectroscopy and PXRD showed no drug-excipient interaction. The lycopene liquisolid compacts passed both pre-compression and post-compression evaluations within acceptable limits.

Conclusion: The formulation batch F-7, formulated with Neusilin US2 as a carrier and 40% drug concentrationshowed 98% in vitro drug release and thus it was selected as the optimized formulation with improved dissolution.

Objectives: This study focused on synthesizing and characterizing novel thiosemicarbazide derivatives containing a 1,2,4-triazole moiety and evaluating their antimicrobial activity against several bacterial strains. The research aimed to identify key structural features that enhance antimicrobial efficacy through structure-activity relationship analysis and identify the minimum inhibitory concentration (MIC) of the most potent compounds to assess their potential for further development as antimicrobial agents.

Materials and methods: Nine novel thiosemicarbazide derivatives containing a 1,2,4-triazole moiety were synthesized by reacting 1,2,4-triazole derivatives with thiosemicarbazide precursors, and the products were characterized using infrared spectroscopy, proton nuclear magnetic resonance (¹H-NMR), carbon-13 nuclear magnetic resonance (¹³C-NMR) spectroscopy, and elemental analysis. The antimicrobial activity of these compounds (5a-i) was tested against Klebsiella pneumoniae (K. pneumoniae),Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa (P. aeruginosa), using microdilution, disk diffusion, and broth microdilution methods. Dimethyl sulfoxide was used as a negative control, and Vancomycin and Meropenem were used as positive controls, with all results converted to µM for consistent analysis.

Results: The synthesized thiosemicarbazide derivatives (5a-i) were confirmed to be structurally correct through Fourier-transform infrared spectroscopy, ¹H-NMR, and ¹³C-NMR spectroscopy. Among the tested compounds, 5e (4-bromophenyl) and 5g (n-propyl) showed significant antimicrobial activity, with 5g exhibiting the strongest effects against S. aureus and P. aeruginosa. Other derivatives, such as 5b (4-NO₂Ph), 5c (4-FPh), and 5d (4-ClPh), showed moderate activity, while no significant activity was observed against K. pneumoniae or E. faecalis.

Conclusion: The study successfully synthesized a series of novel thiosemicarbazide derivatives with a 1,2,4-triazole moiety and evaluated their antimicrobial potential. Compounds 5e and 5g exhibited significant antibacterial activity, particularly against S. aureus and P. aeruginosa, with MIC values in the low micromolar range. These findings suggest that the compounds hold promise as potential antimicrobial agents, and further studies should focus on optimizing their efficacy and exploring their mechanism of action.

Objectives: Norvir^® oral powder [ritonavir (RTV)] employs polyvinylpyrrolidone/vinyl acetate as the polymer to formulate an amorphous solid dispersion. Its oral absolute bioavailability is 70% in the fasted state, and it has negative food effects. The aim of this study was to perform in vitro dissolution of Norvir^® powder and Wagner-Nelson deconvolution of in vivo data under fasted, moderate fat, and high fat conditions in order to elucidate the relevance of in vitro dissolution testing.

Materials and methods: In vitro dissolution of Norvir^® oral powder was conducted, and the human pharmacokinetic data of Norvir^® powder were obtained from literature, under fasted, moderate fat, and high fat conditions. Wagner-Nelson deconvolutions were performed. The absolute fraction absorbed (F_a) profiles were compared to the in vitro dissolution (F_d) profiles. Levy-Polli plot analysis was also conducted. For each pharmacokinetic condition, a scale factor was estimated to approximate the extent to which in vitro dissolution needed to be slowed down to mimic in vivo dissolution.

Results: Qualitatively, there was a large difference between in vitro and in vivo dissolution. In vitro dissolution showed 98% release in 5 minutes. Meanwhile, from Wagner-Nelson analysis, only 5.5% of the drug dissolved (and absorbed) in vivo in 5 min under fasted conditions. It was not until 2 hr that 49% of the RTV dose dissolved (and was absorbed) in vivo. In vivo, moderate fat and high fat conditions were even slower in producing a certain effect. The Levy-Polli plot exhibited a "reverse-L" profile. It was concluded that such rapid in vitro dissolution did not mimic the in vivo dissolution of RTV.

Conclusion: Biopharmaceutic consideration of in vitro dissolution, in vivo pharmacokinetics, and deconvolution analysis indicated that in vitro dissolution was "too rapid" to adequately mimic in vivo dissolution. Findings suggest greater inspection of in vitro methods for poorly water-soluble drugs, especially those drugs where in vivo absorption is expected to be rate-limited by dissolution.