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Type 2 diabetes mellitus is a multifactorial disorder whose primary manifestation usually initiates with elevated blood sugar levels. Several antidiabetic agents are used to manage type 2 diabetes mellitus, of which empagliflozin is an oral sodium-glucose co-transporter (SGLT-2) inhibitor in the kidney. This research aims to develop and validate a simple analytical method for determining empagliflozin levels in biological fluid and to further evaluate grapefruit juice's impact on empagliflozin pharmacokinetics in rats. High-Performance Liquid Chromatography (HPLC) was used to establish a simple, rapid, and accurate method for determining empagliflozin levels in rat plasma, in the presence of grapefruit juice. Four groups of rats (n = 10 rats in each) were used in the preclinical study. Group A (healthy rats) received empagliflozin alone; Group B (healthy rats) received empagliflozin with grapefruit; Group C (diabetic rats) received empagliflozin with grapefruit; and Group D (healthy, negative control) received no medication. The rats (n = 10) were given grapefruit juice instead of water for seven days before receiving the empagliflozin dose (0.16 mg/kg). Some pharmacokinetic parameters for each group were determined. The maximum plasma concentration (Cmax) and area under the curve (AUC) of empagliflozin in Group A without grapefruit intake were 730 ng/mL and 9264.6 ng × h/mL, respectively, with Tmax (2 h). In Group B, Cmax was 1907 ng/mL and AUC was 10,290.75 ng × h/mL in the presence of grapefruit, with Tmax (1 h); whereas, in Group C, the Cmax was 2936 ng/mL and AUC was 18657 ng × h/mL, with Tmax (2 h). In conclusion, our results showed that the co-administration of grapefruit with empagliflozin should be cautiously monitored and avoided, in which grapefruit elevates the plasma level of empagliflozin. This may be attributed to the inhibition of the uridine enzyme in the grapefruit by hesperidin, naringin, and flavonoid. [ABSTRACT FROM AUTHOR]

Twelve healthy eight-week-old male Wistar rats weighing 200 g were used. Rats were chosen randomly, and their tails were identified and separated into cages/groups. The first group received an oral dose of 11.5 mg of levetiracetam in 5 mL of water, and the second group was given date syrup (250 g mixed with 250 mL water) for seven days, then 11.5 mg LEV in 5 mL water on day 7. One week of preadministered date molasses significantly decreased levetiracetam pharmacokinetic parameters in rats, such as Cmax (72 vs. 14 ng/mL, p = 0.01), Tmax (1.78 vs. 0.44 h, p < 0.001), and AUC (880 vs. 258 ng.h/mL, p < 0.001). This decrease in plasma levetiracetam levels caused by date molasses could be attributed to decreased levetiracetam absorption. On the other hand, the current study discovered that rats given date molasses for a week had a reduced rate and extent of absorption. As a result, date molasses might increase the risk of epileptic seizures in oral LEV-treated ones. [ABSTRACT FROM AUTHOR]

Aim: The study evaluated the effect of different concentrations of sildenafil-containing ointment on wound healing in healthy and streptozotocin (STZ)-induced diabetic rats. Methods: A total of 108 Sprague Dawley male rats aged 5 months were randomly divided into two groups: healthy and diabetes-inducing rats. Following induction of diabetes by intraperitoneal STZ injection (55 mg/kg), diabetic and healthy rats were subdivided into six groups (9 rats each). Linear incisions of the dorsal backs of rats were made. Then, rats were treated twice daily with either 2%, 2% + Fucidin, 5% sildenafil-containing ointments, oral sildenafil (13.0 mg/kg), moist exposed burn ointment or vehicle. During treatment, the percent reduction of the wound area and tensile strength were measured on days 3, 7 and 10. Furthermore, histopathology was performed on the wounded skin on similar days for the assessment of collagen synthesis and proliferation of new capillary vessels. Results: In healthy and STZ-induced diabetic rats, the percent reduction in wound area on day 3 was significantly higher in sildenafil-containing ointment-treated groups than all other groups, whereas on day 7 only the 5% sildenafil-containing ointment-treated group showed better response in healthy rats. Although the sildenafil-containing ointment significantly showed better tensile strength than all other groups, the 5% sildenafil-treated group significantly enhanced the tensile better than the 2% and 2% + Fucidin dose. Furthermore, the histological evaluation revealed that sildenafil-containing ointment promoted collagen synthesis and proliferation of new capillary vessels. Conclusion: Our results suggest that sildenafil-containing ointment can provide an advantage in wound healing by promoting wound contractions and resistance to wound breakage in healthy and diabetic conditions. Therefore, 5% sildenafil-containing ointment can be used as a support factor for wound healing in healthy and diabetic conditions; however, clinical trials are required to confirm the benefits of sildenafil in wound healing. [ABSTRACT FROM AUTHOR]

Vitamin D is necessary for maintaining and regulating calcium levels; thus, insufficiency of vitamin D increases the risk of many chronic diseases. This study aimed to examine vitamin D levels among Jordanian and Iraqi volunteers and find the relation between vitamin D level and lipid profile patients. Vitamin D levels were evaluated using enzyme-linked immunosorbent assay. For young healthy group subjects, vitamin D levels were 20.60 ± 5.94 ng/mL for Jordanian and 27.59 ± 7.74 ng/mL for Iraqi. Vitamin D concentrations for young males and females were 25.82 ± 8.33 ng/mL and 21.95 ± 6.39 ng/mL, respectively. Females wearing hijab were 20.87 ± 6.45 ng/mL, while uncovered females were 23.55 ± 6.04 ng/mL. For >40 years Iraqi subjects, vitamin D level for healthy was 29.78 ± 9.49 ng/mL and 23.88 ± 7.93 ng/mL for hyperlipidemic subjects. Vitamin D levels for overweight and obese healthy groups were significantly higher (P<0.050) than those for the hyperlipidemic patients groups. Vitamin D levels for males were significantly higher than females and were significantly higher for healthy than those hyperlipidemic Iraqi patients. These findings showed that vitamin D levels are affected by age, nationality, gender, and health statues and highlight the importance of vitamin D supplementation for groups with low levels particularly old, hijab wearing females, and hyperlipidemic groups. [ABSTRACT FROM AUTHOR]

This study outlines the development of a cost-effective, extended-release febuxostat (FEB) tablet using activated charcoal as an adsorbent to enhance drug release. FEB, a BCS Class II drug, presents formulation challenges due to low solubility and high lipophilicity. We evaluated eight formulations with varying FEB-to-charcoal ratios using FTIR and DSC for physical interactions and followed USP standards for overall assessment. The optimal 1:0.25 FEB-to-charcoal ratio demonstrated a consistent 12 h zero-order release pattern. In vivo studies indicated a significantly extended plasma profile compared to immediate-release tablets. The optimal tablets demonstrated acceptable hardness and disintegration times. This innovative approach enhances patient compliance, improves bioavailability, and reduces production costs, offering a promising solution for controlled FEB delivery. [ABSTRACT FROM AUTHOR]

The two main classifications of antidepressant medications are selective norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs). Out of the available choices, selective serotonin reuptake inhibitors (SSRIs) have emerged as the most commonly prescribed option. The class demonstrates a greater degree of diversity in its structural characteristics in contrast to its neurochemical effects. Nevertheless, it is important to acknowledge that the chemical composition of a drug within this specific class does not carry substantial significance in the selection process. A comprehensive analysis of the pharmacodynamic and pharmacodynamic properties of antidepressant drugs proves advantageous for clinicians and managed care providers responsible for selecting preferred selective serotonin reuptake inhibitors (SSRIs) from a roster of authorized medications. The physicochemical characteristics, which possess considerable significance, are frequently disregarded except during the drug development stage. Pharmacodynamic properties refer to the physiological and biochemical effects that drugs exert on the human body. It is noteworthy that the inclusion of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) in a comprehensive depression management protocol may demonstrate enhanced effectiveness in clinical environments as opposed to controlled trials. [ABSTRACT FROM AUTHOR]

Ribociclib is a newly approved orally administered drug for breast cancer. This study aimed to prepare, characterize, and evaluate hybrid lipid–polymer nanoparticles (PLNs) of ribociclib to enhance its in vitro dissolution rate, pharmacokinetics, and anticancer efficacy. Ribociclib-loaded PLNs were prepared by solvent evaporation using the Box–Behnken design to optimize formulation variables. Particle size, entrapment efficiency, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), in vitro release cytotoxicity, molecular modeling, and pharmacokinetic studies were examined. The ribociclib-loaded PLN (formula 1, F1) was optimized in terms of particle size (266.9 ± 4.61 nm) and encapsulation efficiency (59.1 ± 2.57 mg/mL). DSC and thermogravimetric characterization showed the absence of a crystalline structure in the prepared PLNs, confirmed by FTIR, and showed no interactions between the components and the drug. AFM showed well-dispersed heterogeneously shaped nanoparticles. The in vitro release profile exhibited significant results for the optimized formula, reaching 100% at 600 and 90 min at pH 6.8 and 1.2, respectively. The low IC50 obtained by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay suggests that optimized PLN might serve as an effective delivery vehicle for cancer treatment, especially breast and lung cancer. Molecular modeling revealed several hydrogen bonds. A pharmacokinetic study in rats showed that the ribociclib formula had a 6.5-fold increase in maximum concentration (Cmax) and a 5.6-fold increase in area under the curve (AUC). Regarding the everted intestinal sac absorption, formula 1 increased ribociclib penetration relative to the physical combination and pure medication. In conclusion, optimized PLNs with enhanced physicochemical and cytotoxic properties and improved pharmacokinetic parameters were successfully prepared. [ABSTRACT FROM AUTHOR]

A novel, sensitive, and low-cost HPLC method for the rapid determination of favipiravir (FVR) in rat plasma was developed and validated, and the effect of vitamin C on FVR pharmacokinetic parameters was investigated. FVR and oxcarbazepine (IS) were separated using a mobile phase of 50% acetonitrile and 50% water (with 0.25% trifluoroacetic acid) at 1.0 mL/min flow rate and detected at λmax 289 nm. The intra- and interday values for FVR in plasma were less than 15%, with low, medium, and high QC levels for the relative recovery rate, according to ICH guidelines. Cmax values in the control and experimental groups were 558 ± 124.42 and 979.13 ± 138.10 ng/mL, respectively; t1/2 values were 7.15 ± 1.60 and 9.09 ± 1.14 h, AUC(0-t) values were 5697.70 ± 536.58 and 7381.62 ± 1577.58 ng.h/mL, and AUC(0-∞) values were 5697.70 ± 536.58 and 8192.36 ±  1721.67, respectively. According to the results, the experimental group's Cmax of FVR was 75.17% higher than the control group's, the Vz/F was lower, and the t1/2 was 1.86 h longer. The technique developed for determining FVR in plasma was useful for FVR pharmacokinetics and food–drug interaction investigations. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs are the most commonly prescribed anti-inflammatory drugs worldwide. The most common side effects are gastrointestinal. Pantoprazole, a proton pump inhibitor (PPI), can be used to prevent these events from occurring. In this study, we attempt to develop and validate a novel method for determining and validating the fixed-dose combination of meloxicam and pantoprazole. A new method has been developed and validated to estimate pantoprazole and meloxicam in a fixed-dose combination using RP-HPLC. In order to separate the drugs, a mobile phase phosphate buffer/acetate was used (30:70, v/v), with a pH of 3.4 and a flow rate of 1.0 mL/min at 25 °C. The detection wavelength for the drugs was at a wavelength of 310 nm. The retention times for meloxicam and pantoprazole were 6 and 9 min, respectively. In concentrations ranging from 0.1 to 200 mg/L, the linearity of the detector was established. The r was 0.9998 for both drugs. Recovery rates ranged from 98 to 102% on average. According to the guidelines of the International Council on Harmonization, the results were satisfactory. Using the method presented herein, the pharmaceutical formulation of the combined meloxicam and pantoprazole can be routinely tested. [ABSTRACT FROM AUTHOR]

Abstract: We recently designed a series of N-[4-(t-amino-yl)-but-2-yn-1-yl] isoindoline-1,3-diones as anti-inflammatory compounds, called ZM compounds. These ZM compounds were categorized according to the nature of the cyclic amino groups into ZM2, ZM3, ZM4, and ZM5 and were shown to reduce carrageenan-induced inflammation, inhibit cyclooxygenase (1 and 2) and have less adverse effects than the common non-steroidal anti-inflammatory drugs. In the present study, we are examining the potential effects of ZM compounds in modulating cytokines production in vivo and in vitro from stimulated spleen cells, CD4+ CD25+ve T regulatory cells and CD4+CD25−ve T helper cells. Six hours following oral administration of 20mg/kg of ZM4 and ZM5 compounds reversed LPS-induced TGF-β suppression whereas ZM2, ZM3, ZM4, and ZM5 reversed LPS-induced TNF-α and IL-12 increase in mice spleen. In addition, increasing concentrations of ZM2, ZM4 and ZM5 increased significantly TGF-β1 production, whereas ZM3, ZM4 and ZM5 suppressed only TNF-α production in LPS and LPS+PMA stimulated spleen cells. Furthermore, only ZM5, enhanced significantly TGF-β1 production from LPS and LPS+PMA stimulated CD4+CD25+ve cells (p<0.001), whereas none of the ZM compounds modulated TNF-α from CD4+CD25−ve T helper cells. These results indicate that ZM5 (N-{4-(2-Azepan-1-yl)-but-2-yn-1-yl}isoindoline-1,3-dione) enhances TGF-β production from CD4+CD25+ve cells independent of protein kinase C activation and suggest that all ZM compounds suppress TNF-α from monocytes/macrophage cells. In conclusion, these ZM compounds have potential to be used use as anti-inflammatory agents and further studies to show the possibility of utilizing these basic aminoacetylenic isoindolines in autoimmune mediated inflammatory diseases are warranted. [Copyright &y& Elsevier]

The current study is a randomized, open-label, two-period, two-sequence, two-way crossover pharmacokinetic study in healthy Jordanian subjects to evaluate the pharmacokinetics and bioequivalence profile of two cases of empagliflozin 10 mg under fasting and fed conditions. The plasma concentrations of empagliflozin were determined using an HPLC-MS/MS method. Tolerability and safety were assessed throughout the study. This study included 26 subjects, 26 in both fasting and fed groups.The pharmacokinetic parameters, which included the area under the concentration–time curve from time zero to infinity (AUC0–inf) and the final quantifiable concentration (AUC0–last), maximum serum concentration (Cmax), and time to reach the maximum drug concentration (Tmax) were found to be within an equivalence margin of 80.00–125.00%. The pharmacokinetic profiles show that the empagliflozin test and parent reference cases were bioequivalent in healthy subjects. The two treatments' safety evaluations were also comparable. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hypericin was stably loaded into thermally-activatable liposomes. • Hypericin thermosentitive liposomes have narrow thermosensitivity. • Hyperthermia potentiates the effect of Hypericin mediated photodynamic therapy. • Hypericin thermosensitive liposomes enhanced cellular uptake. • Liposomal Hypericin activated with hyperthermia reduced tumor cells viability. The potent photodynamic properties of Hypericin (Hyp) elicit a range of light-dose-dependent anti-tumor activities. However, its low water solubility hampers its broad application. Therefore, the administration of Hyp into biological systems requires drug carriers that would enable sufficient bioavailability. Stimuli-triggered nanocarriers, which are sensitive to endogenous or exogenous stimuli, have become an attractive replacement for conventional therapeutic regimens. Herein, we produced optimized Hyp thermosensitive liposomes (Hyp-TSL), self-assembled from DPPC, DSPC, DSPE-PEG2000. Hyp-TSL displayed a hydrodynamic diameter below 100 nm with an adequate encapsulation efficiency of 94.5 % and good colloidal stability. Hyp-TSL exhibited thermal sensitivity over a narrow range with a phase transition temperature of 41.1 °C, in which liposomal destruction was evident in AFM images after elevated temperature above the phase transition temperature. The uptake of TSL-Hyp into MDA-MB-231 cells was significantly increased with hyperthermic treatment of 42 °C when compared to the uptake at a average physiological temperature of 37 °C. Consequent enhancement of cellular reactive oxygen species was observed after hyperthermic treatment at 42 °C. The half-maximal inhibitory concentration of Hyp TSL was reduced by 3.8 fold after hyperthermic treatment at 42 °C in comparison to treatment at 37 °C. Hyp-TSL were considered safe for intravenous applications as compared by hemocompatibility studies, where coagulation time was <50 s and hemolytic potential was <10%. Conclusively, the enhancement in tumor drug availability correlated with improved therapeutic outcomes. [ABSTRACT FROM AUTHOR]

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1–60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data's heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday's % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at −20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank. [ABSTRACT FROM AUTHOR]