Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. ...Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Voriconazole an antifungal drug, has a potential for drug-drug interactions (DDIs) with administered drugs. Clarithromycin is a Cytochromes P450 CYP (3A4 and 2C19) enzyme inhibitor, and voriconazole ...is a substrate and inhibitor of these two enzymes. Being a substrate of the same enzyme for metabolism and transport, the chemical nature and pKa of both interacting drugs make these drugs better candidates for potential pharmacokinetic drug-drug interactions (PK-DDIs). This study aimed to evaluate the effect of clarithromycin on the pharmacokinetic profile of voriconazole in healthy volunteers.
A single oral dose, open-label, randomized, crossover study was designed for assessing PK-DDI in healthy volunteers, consisting of 2 weeks washout period. Voriconazole, either alone (2 mg × 200 mg, tablet, P/O) or along with clarithromycin (voriconazole 2 mg × 200 mg, tablet + clarithromycin 500 mg, tablet, P/O), was administered to enrolled volunteers in two sequences. The blood samples (approximately 3 cc) were collected from volunteers for up to 24 h. Plasma concentrations of voriconazole were analyzed by an isocratic, reversed-phase high-performance-liquid chromatography ultraviolet-visible detector (RP HPLC UV-Vis) and a non-compartmental method.
In the present study, when voriconazole was administered with clarithromycin versus administered alone, a significant increase in peak plasma concentration (Cmax) of voriconazole by 52% (geometric mean ratio GMR: 1.52; 90% CI 1.04, 1.55;
= 0.000) was observed. Similarly, the area under the curve from time zero to infinity (AUC
) and the area under the concentration-time curve from time zero to time-t (AUC
) of voriconazole also significantly increased by 21% (GMR: 1.14; 90% CI 9.09, 10.02;
= 0.013), and 16% (GMR: 1.15; 90% CI 8.08, 10.02;
= 0.007), respectively. In addition, the results also showed a reduction in the apparent volume of distribution (Vd) by 23% (GMR: 0.76; 90% CI 5.00, 6.20;
= 0.051), and apparent clearance (CL) by 13% (GMR: 0.87; 90% CI 41.95, 45.73;
= 0.019) of voriconazole.
The alterations in PK parameters of voriconazole after concomitant administration of clarithromycin are of clinical significance. Therefore, adjustments in dosage regimens are warranted. In addition, extreme caution and therapeutic drug monitoring are necessary while co-prescribing both drugs.
clinicalTrials.gov, Identifier NCT05380245.
End-stage renal disease (ESRD) patients are mostly managed with maintenance hemodialysis (MHD). ESRD patients on MHD also present with many complications, such as anemia, hyperparathyroidism, and ...hepatitis prevalence. This study depicts the real-world scenario of anemia among MHD and end-stage renal disease patients in the Pakistani population. A retrospective, multicentric, and real-world data analytical study was conducted at 4 dialysis centers in Pakistan. The study had a sample size of n = 342 patients on maintenance hemodialysis. The data were gathered from the medical records of patients. Data analysis was performed using STATA Version 16. Statistical significance was gauged at a 0.05 level of significance. According to our results, the mean age of the patients was 45 (±15) years. Most of the patients were male (n = 234, 68.4%), whereas 58.1% of the patients were maintained on twice-weekly hemodialysis. The most commonly reported comorbidities were hypertension and diabetes mellitus. The frequency of dialysis (P < 0.01) and comorbidities (P = 0.009) had a significant association with anemia in MHD patients. The majority of the patients had hyperparathyroidism (52%) with anemia. Upon performing binary logistic regression, multivariate analysis displayed a similar odds value for having anemia in patients with every additional month in the duration of hemodialysis (OR 1.01, P = 0.001), the odds of anemic patients having a positive antihepatitis-C antibody (OR 2.22, P = 0.013), and the odds of having anemia in patients in the age category below 45 years (OR 1.93, P = 0.013). In conclusion, the study results depict that every additional month in the duration of hemodialysis, age (<45 years), and positive anti-HCV antibody status, these variables were more likely to have anemia in our study MHD patients. While in our final multivariate model, no statistically significant association was observed between hyperparathyroidism and anemia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Adsorption techniques are widely used to remove pollutants from wastewater; however, composites are gaining more importance due to their excellent adsorption properties. Bentonite composite with ...Eriobotrya japonica seed was prepared and used for the adsorption of copper (Cu) metal from aqueous media. The process variables such as pH, Cu(II) ions initial concentration, adsorbent dose, contact time and temperature were optimized for maximum Cu(II) adsorption. At pH 5, adsorbent dose 0.1 g, contact time 45 min, Cu(II) ions initial concentration 75 mg/L and temperature 45 °C, maximum Cu(II) adsorption was achieved. Desorption studies revealed that biocomposite is recyclable. Langmuir, Freundlich and Harkins-Jura isotherms as well as pseudo-first and pseudo-second–order kinetics models were applied to understand the adsorption mechanism. Thermodynamic parameters (ΔG0, ΔH0 and ΔS0) suggest that the adsorption process was spontaneous and endothermic in nature. The pseudo-second-order kinetic model and Langmuir isotherm fitted well to the adsorption data. Results showed that biocomposite was more efficient for Cu(II) adsorption in comparison to individuals native Eriobotrya japonica seed biomass and Na-bentonite.
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•Biocomposite was prepared from bentonite and E. japonica seed powder.•Biocomposite was used for copper adsorption and process variables were optimized.•Isotherms, kinetics, thermodynamics and desorption studies were performed.•Biocomposite affinity for copper was excellent versus native biomass and bentonite.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
In this research work, an isocratic, reversed-phase high-performance liquid chromatography-ultraviolet/visible detector method was developed for analysis of voriconazole standard ...(stock-solution) and in plasma samples. Optimization and validation of the method was carried out as per international guidelines. The method offered a simple liquid–liquid extraction technique, which exhibited best recovery of voriconazole along with fluconazole, i.e., internal standard. Different experimental conditions were tried and ultimately, the best outcomes were accomplished utilizing C-18 Perkin-Elmer® column with particulars of 150 mm length, 4.6 mm inner diameter and 5 μm particle size, protected by an RP-18 Perkin-Elmer® Pre-column guard cartridge with specifications of 10 μm particle size, 30 mm length and 4.6 mm inner diameter, utilizing mobile-phase of acetonitrile-water (ACN: H2O) in proportion of 60: 40 v/v, having a flow rate of 1.5 mL/min, and wavelength of 254 nm. All the analytes were observed to be separated in ≤7 min. A linear calibration curve was obtained at concentration range of 01–10 μg/mL of voriconazole. The correlation coefficient of voriconazole was observed to be 0.999, and average recovery (in percent) was 97.4%, whereas the relative standard deviation value was ≤2%. The lower limit of detection was 0.01 μg/mL, whereas, lower limit of quantification was 0.03 μg/mL, respectively. This developed method provided outstanding results of all validation parameters, i.e., recovery, accuracy, selectivity, precision and reproducibility. The method proposed for voriconazole analysis was applied effectively for further research investigation of voriconazole in human-plasma samples (to assess the pharmacokinetic parameters), pharmaceutical formulations and pharmacokinetic drug–drug interaction’s.
Palynomorphic studies of 65 common mellitophilous and 16 allergenic flora of Arid and Northern irrigated agroecological zones of Pakistan are carried out in this study by using field emission ...scanning electron microscope (FESEM). Mellitophilous pollen were extracted from honey samples of selected sites. For collection of local allergenic pollen, previously identified allergy‐causing plants were selected. Pollen morphological examination was carried out under FESEM. Diverse range of pollen shapes ranging from monad to polyad and sculpturing ranging from psilate to echinate, scabrate to reticulate, bireticulate, or echinolophate were observed. Brassicaceae, Myrtaceae, Asteraceae, Rosaceae, and Poaceae were observed to be dominant allergenic and mellitophilous families of the selected sites.
Allergenic pollen and honey samples collection
Melliferous pollen extraction from honey samples
Allergenic and melliferous pollen preparation for field emission scanning electron microscope (FESEM) studies
Taxonomic studies of allergenic and melliferous pollen and their sculpturing using FESEM
Development of detailed allergenic and melliferous pollen spectrum
Diverse range of the pollen shapes were observed ranging from monad to polyad
Pollen sculpturing ranging from psilate to echinate, scabrate to reticulate, bireticulate or echinolophate were observed.
Brassicaceae, Myrtaceae, Asteraceae, Rosaceae, and Poaceae families were observed to be dominant allergenic and mellitophilous families of arid and northern irrigated agro ecological zones of Pakistan
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The current study describes ethnobotanical (EB) and traditional ethnomedicinal (TEMs) uses of medicinal plants (MPs) of Tehsil Samahni area of Azad Jammu and Kashmir, Pakistan. Indigenous inhabitants ...of the area mostly reside in remote mountainous areas and depend on wild plants for life necessities and treatment of different diseases. This paper presents first quantitative ethnobotanical study describing the popularity level of MPs in indigenous communities by using relative popularity level (RPL) and rank order of priority (ROP) indices. The data of TEMs and EB uses were collected from 200 interviewees consisting of traditional herbal practioners (110) and farmers (90) from study area using structured and semi-structured interview methodology during year 2019. It was found that illiterate peasants have more knowledge and practice of TEMs than other people. A total of 150 plant species belonging to 58 families with botanical and local names, parts used, mode of recipes preparation, administration mechanism and TEMs uses were documented in systematic manner. It was explored that highest number (7.69%) of plants of Moraceae were used in TEMs and followed by species of Asteraceae (6.29%). The ethnobotanical data was analyzed by using quantitative ethnobotanical tools viz: informant consensus factor (ICF), fidelity level (FL), relative frequency of citation (RFC), use value index (UVI), relative importance of plants (RIP), relative populatiry level (RPL) and rank order of popularity (ROP). The leaf ranked first (36.49%) and fruit 2nd (12.07%) being used in TEMs while prevalent use-form was decoction (29.28%), followed by tea (23.05%) and preferably taken as oral (46.66%). ICF analysis proved that diabetes, hypertension, rabies, snake sting and joint pains were the most prevalent occurring infirmities. The highest RFC (0.95) was found for Acacia modesta, followed by Boerhavia procumbens (RFC:0.87) and Berberis lycium (RFC:0.85). The relative importance of MPs was calculated by using UVI and Moringa oleifera showed highest (1.38), followed by Zanthoxylum armatum (1.25) and Withania somnifera (1.24) use-values. High UVI of plants depicts that these species are predominantly used in local health care system. The plants Phyllanthus emblica, Morus macruora, Justicia adhatoda and Melia azedarach depicted high values (1.00) of FL and RPL proving that these taxa are commonly used in indigenous medicines by local inhabitants and have better potential for drug discovery by ethnopharmacological analysis. Out of total, 26 species had more than 50% ROP index and Phyllanthus emblica and Flacourtia indica (ROP = 100) followed by Morus macruora (ROP: 97) were used to cure 'hypertension and hyperlipidemia' and 'cough, chest infection', respectively. It was found that 30% of total species were previously reported as medicinal while 70% plants were first time reported to be used in TEMs and authenticated by using of quantitative ethnobotanical tools. Ethnopharmacological potential of indigenous plants was confirmed by RIP and RPL indices which had been used to cure one or more body systems and were promulgated in the local herbal medicine system. The research provides clues to screen these plant species by using latest phytochemical and pharmacological analysis for novel drug discovery. This study will also be useful for conservation of bioculture traditional knowledge of indigenous communities and the most important is to conserve medicinal plants of the study area for future generations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The study assessed the health risks associated with heavy metal ingestion and explored the use of honey bee products as a bio-indicator for heavy metal pollution. All honey bee products tested showed ...heavy metals, but some honey samples had concentrations exceeding permissible limits for Cd, Pb, Ni, and Cr. The mean concentrations of heavy metals (mg/kg) in the honey, propolis, bee wax, and bee pollen were Fe (1.32) > Zn (1.31) > Pb (0.46) > Ni (0.18) > Cr (0.16) > Cu (0.14) > Co (0.12) > Mn (0.05) > Cd (0.03), Fe (8) > Zn (1.13) > Mn (0.59) > Pb (0.13) > Ni (0.07) > Cu (0.06) > Co (0.05) > Cr (0.03) > Cd (0.02), Fe (1.31) > Pb (0.41) > Ni (0.407) > Zn(0.25) > Mn (0.12) > Co(0.10) > Cu (0.07) > Cr (0.05) > Cd (0.002), and Fe (2.2) > Zn (0.75) > Ni (0.25) > Pb (0.16) > Cu (0.05) > Mn (0.045) > Co (0.04) > Cr (0.01) > Cd(0.002), respectively. Similarly, the mean concentration of heavy metals (mg/kg) in the soil, flowers and pine pollen was Fe (539.08) > Zn (89.53) > Mn (66.91) > Ni (58.5) > Co (19.2) > Cr (11.42) > Pb (6.58) > Cu (5.71) > Cd (0.19), Fe (3.12) > Zn (0.95) > Mn (0.72) > Ni (0.29) > Cu (0.16) > Cr (0.14) > Pb (0.059) > Co (0.057) > Cd (0.003) and Fe (2.59) > Zn (1.75) > Mn (0.43) > Pb (0.34) > Co (0.1) > Cr (0.07) > Cu (0.06) > Cd (0.039) > Ni (0.03), respectively. The atomic absorption spectrophotometry procedure was validated through a recovery study and achieved accuracy through the limit of detection (LOD) and limit of quantification (LOQ). The mean Bio concentration factor (BCF) indicated that the transfer from soil to honey was higher than from soil to flower. The metal pollution index (MPI) of the selected indicators was in descending order: soil > honey > flowers > propolis > pine pollen > beeswax > bee pollen. The hazard quotient (HQ) and hazard index (HI) were below one, showing no chronic health risk. The carcinogenic risk (CR) of Cd, Cr, and Ni in honey for children, male and female adults for the consumers exceeds the acceptable level, making Cd, Cr, and Ni the most concerning heavy metals in honey. The study suggests that regular monitoring of heavy metal pollution is essential.The study assessed the health risks associated with heavy metal ingestion and explored the use of honey bee products as a bio-indicator for heavy metal pollution. All honey bee products tested showed heavy metals, but some honey samples had concentrations exceeding permissible limits for Cd, Pb, Ni, and Cr. The mean concentrations of heavy metals (mg/kg) in the honey, propolis, bee wax, and bee pollen were Fe (1.32) > Zn (1.31) > Pb (0.46) > Ni (0.18) > Cr (0.16) > Cu (0.14) > Co (0.12) > Mn (0.05) > Cd (0.03), Fe (8) > Zn (1.13) > Mn (0.59) > Pb (0.13) > Ni (0.07) > Cu (0.06) > Co (0.05) > Cr (0.03) > Cd (0.02), Fe (1.31) > Pb (0.41) > Ni (0.407) > Zn(0.25) > Mn (0.12) > Co(0.10) > Cu (0.07) > Cr (0.05) > Cd (0.002), and Fe (2.2) > Zn (0.75) > Ni (0.25) > Pb (0.16) > Cu (0.05) > Mn (0.045) > Co (0.04) > Cr (0.01) > Cd(0.002), respectively. Similarly, the mean concentration of heavy metals (mg/kg) in the soil, flowers and pine pollen was Fe (539.08) > Zn (89.53) > Mn (66.91) > Ni (58.5) > Co (19.2) > Cr (11.42) > Pb (6.58) > Cu (5.71) > Cd (0.19), Fe (3.12) > Zn (0.95) > Mn (0.72) > Ni (0.29) > Cu (0.16) > Cr (0.14) > Pb (0.059) > Co (0.057) > Cd (0.003) and Fe (2.59) > Zn (1.75) > Mn (0.43) > Pb (0.34) > Co (0.1) > Cr (0.07) > Cu (0.06) > Cd (0.039) > Ni (0.03), respectively. The atomic absorption spectrophotometry procedure was validated through a recovery study and achieved accuracy through the limit of detection (LOD) and limit of quantification (LOQ). The mean Bio concentration factor (BCF) indicated that the transfer from soil to honey was higher than from soil to flower. The metal pollution index (MPI) of the selected indicators was in descending order: soil > honey > flowers > propolis > pine pollen > beeswax > bee pollen. The hazard quotient (HQ) and hazard index (HI) were below one, showing no chronic health risk. The carcinogenic risk (CR) of Cd, Cr, and Ni in honey for children, male and female adults for the consumers exceeds the acceptable level, making Cd, Cr, and Ni the most concerning heavy metals in honey. The study suggests that regular monitoring of heavy metal pollution is essential.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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