Turkish Journal of Pharmaceutical Sciences最新文献

Objectives: A new, simple, and affordable spectrofluorimetric method was established for quantification of capecitabine in bulk and in marketed formulations.

Materials and methods: Native fluorescence of capecitabine in 0.1% (w/v) cetrimide was measured at 386 nm after excitation at 313 nm.

Results: A linear relationship between fluorescence intensity and capecitabine concentration was noticed in 0.2-1.0 μg/mL range. The method was supported by checking several validation parameters as stated using International Conference on Harmonization (ICH) guidelines. The limit of detection (LOD) and quantification (LOQ) values (0.032 and 0.096 μg/mL, respectively) and results of validation parameters demonstrated that the method procedure were sensitive, accurate, precise, and reproducible (% relative standard deviation <2.0). The percentage assay in commercial formulation was found to be 99.2, which agrees with ICH guidelines.

Conclusion: Due to the above findings, developed method can be successfully adopted for routine analysis of capecitabine in pharmaceutical dosage forms.

Objectives: Various pure rosemary essential oil containing commercial products are in demand for their health-promoting and cosmetic claims in Türkiye. Although they are natural and harmless, they should be in compliance with European Pharmacopoeia (EP) criteria. Therefore, in this study, 15 rosemary oil samples sold in pharmacies, herbal shops, and online platforms in Türkiye were investigated in terms of "Rosemary Oil" EP 10.0. monograph criteria. In the current study, we aimed to evaluate the current quality status of rosemary essential oils in the Turkish market.

Materials and methods: Appearance, fatty oils and resinified essential oils, relative density, refractive index, optical rotation, and acid value tests were performed according to EP 10.0 and compared with the given standards. In addition, thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) analysis were conducted on all samples for advanced understanding of their phytochemical profile and harmony with EP standards.

Results: Fifteen pure rosemary oil-containing products from the Turkish market were evaluated. All of the samples were licensed as cosmetic products in Türkiye via the Ministry of Health. 83.1 to 96.9% of the ingredients of all samples were determined via GC-MS analysis. Results demonstrated that none of the samples from the Turkish rosemary essential oil market fully complied with the EP rosemary oil monograph standards.

Conclusion: Considering our data, it was revealed that enhanced regulations and auditing mechanisms are needed to improve the quality of products. When the difference between the sources of purchase is assessed, pharmacies are still better locations to obtain such products.

Objectives: Solanum scabrum Mill. commonly "African nightshade" or "huckleberry" is a plant, whose leaves are used by tribes in Nigeria and Cameroon for making the popular "Kombi" and "Njama Njama" soups, respectively. This study aimed to evaluate the anti-inflammatory and anticancer activities of the leaf crude methanol extract from S. scabrum.

Materials and methods: Fractions of the plant were tested for anti-inflammatory potential and in vitro anticancer activity on MCF-7 and HMVII cell lines by carrageenan-induced oedema in mice, and cytotoxicity assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, transwell migration and invasion assays, and apoptosis study by flow cytometry, respectively.

Results: Bioguided isolation yielded a white crystalline compound 3-nitro dibenzofuran (C₁₂H₇NO₃, m/z; 213.19 g/mol, m.p.; 181.49 °C). ¹H-NMR showed seven signals at δ (ppm) 2.8-4.3 consisting of two doublets and five singlets, while ¹³C-NMR revealed twelve carbons, which are majorly methyl carbons at δ (ppm) between 120 and 195. All tested samples demonstrated dose-dependent anti-inflammatory activity in carrageenan-induced mice. The isolated compound, i.e. solanine, and chitosan-loaded drugs showed significant inhibitory activity on the cell lines with inhibitory concentration 50 (IC₅₀) values of 8.52, 0.82, and 22.1 μg/mL, respectively on MCF-7 cell line and 4.54, 0.08, and 12.1 μg/mL, respectively, on HMVII cell line, while doxorubicin (adriamycin) positive control, had IC₅₀ values of 0.02 and 0.06 μg/mL, respectively, on MCF-7 and HMVII cancer cells. Selectivity index of solanine was the lowest in the study, hence, it lacks the ability to differentiate between cancerous and normal cell Vero E6 cell lines. Chitosan-loaded drugs quicken early apoptosis and sustained late apoptosis in cells with much improved selective indices.

Conclusion: The results obtained from this study further affirmed the use of chitosan nanoparticles as carriers for anticancer drugs.

Objectives: Tranexamic acid (TXA) is used systemically to stop bleeding, but it can lead to thromboembolism. Trials have revealed the efficacy of topical TXA on local hemorrhages. However, there is a need for an efficient delivery system that can keep the drug at the site of action.

Materials and methods: To develop a gel containing TXA (3%) optimized in terms of viscosity and dispersibility, the central composite design based on two factors-three levels [carbopol 940 and hydroxypropyl methylcellulose (HPMC), 1-1.5% and 1-2%, respectively] was applied. The spreadability and viscosity were assessed using glass slide and rheometer, respectively. To confirm the compatibility of TXA with the gel, fourier transform-infrared (FTIR) spectroscopy was performed. Drug content uniformity was analyzed by a spectroscopy method. An ex vivo mice model using Franz cells was applied to evaluate the permeation of TXA through the skin. To investigate the effect of topical TXA gel on bleeding time, IVY human method was performed.

Results: HPMC/carbopol 940 (1:1, w/w) gel showed the highest quality in terms of viscosity and dispersibility (3.982 ± 17.6 and 6.052 ± 3.562, respectively). FTIR absorption spectrum showed that all the TXA index peaks appeared without displacement. The complete-encapsulated TXA content was uniformly dispersed throughout the gel. In vitro TXA cumulative release reached 90% in 4 h. The bleeding time determined in vivo for TXA gel was significantly lower than that for TXA solution and control.

Conclusion: The results confirm the importance of further studies on this formulation as a potential medication to stop acute superficial bleeding.

Objectives: The current study goal was to create a precise, sensitive, and validated reverse phase-high performance liquid chromatography (RP-HPLC) method for assessing the direct-acting antiviral daclatasvir (DCV) as well as to evaluate the stability of DCV in both drug and tablet formulations. The current investigation was to display stability indicating methods under different stress conditions, including hydrolysis (acidic, basic, and neutral), oxidation, and photolysis.

Materials and methods: All experiments were performed on HPLC Agilent 1100 with a stainless steel Hypersil C₁₈ column having a particle size of 5 μm and a dimension of 4.6 x 250 mm. The mobile phase chosen was acetonitrile: 0.05% o-phosphoric acid (50:50 v/v) in isocratic mode with 0.7 mL/min flow rate and wavelength 315 nm was selected for detection.

Results: This method was validated for linearity and range, accuracy, precision, limit of detection, limit of quantification, and robustness in accordance with International Council for Harmonisation (ICH) requirements. The results were satisfactory. It was observed that retention time (t_R) was 3.760 ± 0.01 min. In acidic conditions, DCV degradans show t_R at 3.863, 4.121, and 4.783 min and tandem mass spectrometry (MS/MS) spectra scans had m/z 339.1, 561.2 fragment ions. In basic condition, DCV degradans show t_R at 5.188, 5.469 min and MS/MS spectra scans having m/z 294.1, 339.1, 505.2, 527.2 fragment ions. In oxidation conditions, DCV degradans shows t_R at 4.038 min and MS/MS spectra scans having m/z 301.1 and 339.1 fragment ions were observed.

Conclusion: All the mass fragments exhibited additional degradation observed for different stress conditions. This will help to identify the structure of the degradant and its pathways. No degradation was observed in neutral and photolytic conditions.

The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for histone deacetylase (HDAC) inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anticancer activity. We have selected a dataset from earlier research findings. The target and ligand molecules were procured from recognized databases and incorporated into pivotal findings such as molecular docking (XP glide), e-pharmacophore study and 3D QSAR model designing study (phase). Docking revealed molecule 39 with better docking score and well binding contact with the protein. 3D QSAR analysis, which was performed for partial least squares factor 5 reported good 0.9877 and 0.7142 as R2 and Q2 values and low standard of deviation: 0.1049 for hypothesis AADRR.139. Based on the computational outcome, it has been concluded that molecule 39 is an effective and relevant candidate for inhibition of HDAC activity. Moreover, these computational approaches motivate to discover novel drug candidates in pharmacological and healthcare sectors.

Objectives: Analytical method development and validation for determination of favipiravir (FVPR) in pure and tablet dosage forms by liquid chromatography with tandem mass spectrometry/mass spectrometry (LC-MS/MS) technique.

Materials and methods: A simple LC-MS/MS method was developed for determination of a new antiviral drug, FVPR in pharmaceutical formulations. The stationary phase employed was a Shim pack GISS, C₁₈ (100 mm × 2.1 mm, 1.9 μm) column and mobile phase used in pump A was 10.0 mM ammonium acetate and in pump B methanol was used. The gradient program was used with fixed mobile phase flow rate at 0.4 mL min^-1. Total run time was 5.0 min. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines. The established method found better outcomes.

Results: The linearity graph was found in the range of 50-200 μg/mL and the correlation coefficient value (R²) obtained was found to be 1.0. The limit of detection (LOD) and limit of quantification (LOQ) were 4.044 μg/mL and 12.253 μg/mL, respectively. Tremendous recovery outcomes were observed and found to be 101%, 99.0%, and 99.5% for FVPR at 150% upper, 100% middle, and 50% lower concentrations, respectively.

Conclusion: All outcomes obtained comply with ICH guidelines. The developed method was simple, unique, accurate, robust, precise, and reproducible for determination of FVPR in tablet formulation. The method is novel and could be adopted in formulation industry.

Objectives: To determine the prevalence and type of medication discrepancies and factors associated with unintentional discrepancies and identify the rate of hospital readmission and emergency service visit within 30 days after discharge among hospitalized patients with infectious diseases and receiving clinical pharmacist-led medication reconciliation during the coronavirus disease-2019 (COVID-19) pandemic.

Materials and methods: This observational study was conducted in the internal medicine and infectious diseases wards of a tertiary university hospital between July 2020 and February 2021 among hospitalized adult patients with infectious diseases. Medication reconciliation service (including patient counseling) was provided in person or by telephone. The number and type of medication discrepancies detected during the medication reconciliation services, the acceptance rate of pharmacists' recommendation, and factors associated with having at least one unintentional medication discrepancy at admission were evaluated. At follow-up, hospital readmission and emergency service visit within 30 days after discharge were assessed by telephone.

Results: Among 146 patients, 84 (57.5%) had at least one unintentional discrepancy at admission. Only three unintentional discrepancies were determined in three patients at hospital discharge. All the pharmacists' recommendations for medication discrepancies were accepted by the physicians. Having COVID-19 [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.15-4.40; p<0.05], being at a high risk for medication error (OR: 2.01, 95% CI: 1.03-3.92; p<0.05), and higher number of medications used at home (OR: 1.41, 95% CI: 1.23-1.61; p<0.001) were associated with having at least one unintentional discrepancy at admission. The rates of 30 day hospital readmission and admission to the emergency medical service were 12.3% and 15.8%, respectively.

Conclusion: Medication reconciliation service provided by in-person or by telephone was useful for detecting and solving unintentional medication discrepancies during the COVID-19 pandemic.

Objectives: We developed original thermoreversible (sol-gel) formulations of salmon calcitonin (sCT) for nasal applications. The sol-gel has been compared with commercial intranasal sprays in vitro and in vivo studies. The aim of studying sol-gel form is to arrange the viscosity of formulations for a reversible adequate fluidity at different temperatures. This situation may facilitate the use of drugs as sprays and increase the bioadhesive ability to mucosa.

Materials and methods: Characterization of optimum formulations was studied. Validated analytical assays determined the number of sCT. An approximately equal number of commercial and sol-gel dosages were sprayed into the nostrils of the rabbits. Blood samples were collected from the ear veins of rabbits and determined by enzyme immunoassay plates. These plates were evaluated by Thermo Labsystem Multiscan Spectrum at 450 nm. Thanks to Winnonlin 5.2, pharmacokinetic data were evaluated by a non-compartmental method.

Results: The absolute bioavailability of the formulation at pH 4 and the commercial product (CP) was compared by evaluating the primary pharmacokinetic data area under the curve 0→t_last. The absolute bioavailability of the commercial intranasal spray was measured 1.88 based on maximum concentration (C_max) assessment. C_max of the sol-gel formulation pH 4 was calculated as 0.99 and the relative bioavailability was obtained 53.3%.

Conclusion: In vivo pharmacokinetic data of sol-gel formulation with pH 3 showed significantly higher volume of distribution parameter than the CP (111167>35408). It is thought that the formulation adhered to the nasal mucosa releases sCT slowly and less.

Objectives: Mouth ulcers are one of the most prevalent conditions that can be caused by a range of circumstances. Many formulations, such as solutions, suspensions, and ointments are available commercially. However, because there is no long-term effect, no medication can be regarded as totally effective for treating mouth ulcers. The use of bioadhesive methods can boost the therapy efficacy. Because it is easier to administer than prepared gel formulations, the phenomenon of the sol-to-gel conversion can be beneficial. The major goal of this study was to develop and test in situ gels for treating mouth ulcers using choline salicylate and borax as model medicines.

Materials and methods: Because a thermosensitive polymer was employed in this formulation, the sol-to-gel change was thermally reversible, and the frequency of administration was reduced by using the mucoadhesive polymer carbopol. Gelation temperature, pH, gel strength, spreadability, in vitro mucoadhesion, and in vitro drug release were all measured in the formulations.

Results: The experimental section indicated that viscosity of sols and gel strength increased with increasing temperature, i.e., gel can be created at the site of application owing to body temperature. When poloxamer 407 was used at a concentration of 14 to 16 percent w/v, the gelling temperature was close to the body temperature (35-38 °C), but when carbopol 934P was added, the gelling temperature was raised. All formulations had pH between 5.5 and 6.8. All formulations had viscosities of less than 1000 cps, allowing for simple administration of the formulation to a mouth ulcer.

Conclusion: As a result, a correctly developed in situ gel for oral ulcers can extend the duration spent at the application site and minimize the frequency of administration. These findings show that the developed technology is a viable alternative to traditional drug delivery systems and can help patients comply.