Effects of Resveratrol Co-Administration on Celecoxib Disposition and Pharmacokinetics in Healthy Volunteers.

The objective of the current study was to investigate the effects of resveratrol (RSV), a natural herbal remedy used as an adjacent anti-inflammatory supplement on, the pharmacokinetics of celecoxib in healthy male volunteers. Twelve healthy human participants were involved in two-period open-labeled trial. Celecoxib (200 mg) was given as a single oral dose under fasting conditions as a control phase. Afterward, RSV (500 mg) commenced as a single oral dose for ten days as a treatment phase. Blood samples were collected during the control and treatment phases and analyzed using the validated High-performance liquid chromatography (HPLC) method. RSV pre-exposure significantly increased the area under the curve (AUC0-24), peak plasma concentration (Cmax), absorption rate constant (ka), and prolongated half-life (t1/2), along with a decrease in elimination rate constant (ke). Meanwhile, the volume of distribution (Vd/F) and apparent total body clearance (CL/F) were significantly decreased for celecoxib. There was no significant change in the time it takes for celecoxib to reach the maximum concentration (tmax) was observed. The obtained results suggested the presence of a beneficial pharmacokinetic interaction between RSV and celecoxib. Consequently, combining resveratrol as an herbal remedy and celecoxib as an anti-inflammatory drug may synergistically reduce inflammation and osteoarthritis with minimal side effects.

Nano-crystallization of flubendazole for enhanced dissolution rate and improved in vivo efficacy against Trichinella spiralis.

The aim was to enhance the dissolution rate and in vivo efficacy of flubendazole against trichinella spiralis. Flubendazole nanocrystals were developed by controlled anti-solvent recrystallization. Saturated flubendazole solution was prepared in DMSO. This was injected into phosphate buffer (pH 7.4) containing Aerosil 200, Poloxamer 407 or sodium lauryl sulphate (SLS) while mixing using paddle mixer. The developed crystals were separated from DMSO/aqueous system by centrifugation. The crystals were characterized using DSC, X-ray diffraction and electron microscopy. The crystals were suspended in Poloxamer 407 solution and dissolution rate was monitored. Optimal formulation was administered to Trichinella spiralis infected mice. Administration protocol attacked the parasite in intestinal, migrating and encysted phases. The crystals were spherical nanosized with formulation employing 0.2% Poloxamer 407 as stabilizer being optimum with size of 743.1 nm. DSC and X-ray supported particle size reduction with partial amorphization. Optimal formulation showed fast dissolution to deliver 83.1% after 5 min. Nanocrystals provided complete eradication of intestinal Trichinella and reduced larval count by 90.27 and 85.76% in migrating and encysted phases compared with marginal effect in case of unprocessed flubendazole. The efficacy was clearer from improved histopathological features of the muscles. The study introduced nano-crystallization for enhanced dissolution and in vivo efficacy of flubendazole.

Green polymer altered in-situ gel oral liquid sustainable release preparation of vildagliptin suitable for dysphagic diabetic patients: assessment in-vitro & in-vivo.

PURPOSE: This work aimed to fabricate alginate based in-situ gelling matrix of vildagliptin improved by calcium and carboxy methyl cellulose (CMC) for appropriate adjustment of the onset and duration of action. This easy-to-swallow thickened liquid preparation aimed to improve compliance for dysphagic or elderly diabetic patients. METHODS: Vildagliptin dispersions containing alginate were fabricated in the presence or absence of calcium chloride to assess the effect of calcium ion, then a matrix containing 1.5% w/v of sodium alginate with calcium was further examined after the addition of CMC with different concentrations ranging from 0.1% to 0.3%. The viscosity, gelling forming property, Differential scanning calorimetry, and in-vitro drug release were assessed before monitoring the hypoglycemic effect of the selected formulation. RESULTS: In-situ gel matrixes were fabricated at gastric pH with and without calcium ions. The best formula concerning viscosity and the gel-forming property was achieved with higher CMC concentrations, which in turn decreased the rate of vildagliptin release in stimulated gastric pH. In-vivo results confirmed the extended hypoglycemic effect of the vildagliptin in-situ gelling matrix compared to the vildagliptin aqueous solution. CONCLUSION: This study represents a green polymeric-based in-situ gel as a liquid oral retarded release preparation intended for reducing dose frequency, easier administration of vildagliptin, and improving compliance in geriatric and dysphagic diabetic patients.

Changes in dietary habits during Covid-19 lockdown in Egypt: the Egyptian COVIDiet study.

PURPOSE: COVID-19 lockdown changed social habits and lifestyle, including dietary habits, of people worldwide. However, limited information is available about these changes in Egypt. This cross-sectional study investigates the effects of COVID-19 lockdown on dietary habits among the Egyptian populations. METHODS: An online questionnaire, based on sociodemographic data and dietary adherence in accordance with the validated PREDIMED MedDiet Adherence Screener (MEDAS), was used all over the Egyptian governorates. The dietary changes were statistically evaluated for significance in relation to age, gender, body mass index (BMI), education level and governorates. RESULTS: A total of 1010 participants (76% aged below 36 years, 77% female, 22% obese, and 62% university-level education) answered the questionnaire. Respondents ≤ 20 years had a significant increase in weight and consumption of carbonated beverages, commercial pastries, fried and fast food. Egyptians > 50 years old had a significant decrease in physical activity. Underweight people (less than 3% of participants) increased their fast food intake with a prominent rise in weight. However, obese people increased cooking frequency and increased eating times with a decrease in physical activity. Male participants reported increased intake of carbonated beverages and fast food, while female participants increased the intake of homemade pastries with a significant decrease in physical activity. Approximately 50% of participants with postgraduate education reported decreased intake of fast food and carbonated beverages as well as decreased body weight. Residents of Cairo showed a significant increase in vegetable intake, and fried food intake with a decrease in seafood consumption. Participants from the Delta region had a significant increase in pastries intake. CONCLUSION: The findings of this study explored the need for increasing awareness about healthy lifestyle in future lockdown periods.

Patient-friendly extemporaneous formulation of bisoprolol: application to stability and bioavailability studies.

Community and hospital pharmacists always face the challenge to prepare oral liquid extemporaneous formulations to fit the needs of a specific patient population when commercial forms or the required strength is unavailable. This study was performed to prepare a stable patient-friendly oral liquid extemporaneous formulation of bisoprolol. Eight different extemporaneous formulations were prepared using various suspending agent(s). The in vitro dissolution of all extemporaneous formulations was examined. A comprehensive accelerated stability study was carried out to evaluate the adequate beyond-use date of the most optimized extemporaneous formulation. A validated ultra-performance liquid chromatography method was used for the analysis and quantification of bisoprolol in the accelerated stability and bioavailability studies. A group of eight healthy volunteers was enrolled in a two-way cross-over experimental design to study the bioavailability of the most optimized extemporaneous formulation. The pharmacokinetic parameters of bisoprolol were estimated. Extemporaneous suspension containing 0.5% w/v xanthan gum was easily prepared with a simple, natural, safe, sugar-free excipients. It achieved the best dissolution behavior among other extemporaneous suspensions. It was an easily pourable viscous suspension with no sedimentation. At least 98% of the initial concentration of bisoprolol remained throughout the 6-month study period in the selected suspension regardless of the storage conditions. There was no perceptible change in color, odor, or taste, and no noticeable microbial growth was observed in any sample. The selected formulation was bioequivalent to the commercial tablet in terms of the rate and extent of absorption. This research may be of great help during development of appropriate extemporaneous formulation of bisoprolol fumarate. The simple preparation method could be utilized to draw up a standard operating procedure (SOP) easy to use by different types of pharmacy settings.

Towards novel nano-based vaccine platforms for SARS-CoV-2 and its variants of concern: Advances, challenges and limitations.

Vaccination is the most effective tool available for fighting the spread of COVID-19. Recently, emerging variants of SARS-CoV-2 have led to growing concerns about increased transmissibility and decreased vaccine effectiveness. Currently, many vaccines are approved for emergency use and more are under development. This review highlights the ongoing advances in the design and development of different nano-based vaccine platforms. The challenges, limitations, and ethical consideration imposed by these nanocarriers are also discussed. Further, the effectiveness of the leading vaccine candidates against all SARS-CoV-2 variants of concern are highlighted. The review also focuses on the possibility of using an alternative non-invasive routes of vaccine administration using micro and nanotechnologies to enhance vaccination compliance and coverage.

Development of Cyclodextrin-Functionalized Transethoniosomes of 6-Gingerol: Statistical Optimization, In Vitro Characterization and Assessment of Cytotoxic and Anti-Inflammatory Effects.

The poor solubility and stability of 6-gingerol (6-G) could hamper its clinical applications. The aim of the current study was to develop a novel ultra-deformable cyclodextrin-functionalized transethoniosomes (CD-TENs) as a promising delivery system for 6-G. Transethoniosomes (TENs) are flexible niosomes (NVs) due to their content of ethanol and edge activators (EAs). CD-functionalized nanoparticles could improve drug solubility and stability compared to the corresponding nanovesicles. 6-G-loaded ethoniosomes (ENs) were formulated by the ethanol injection technique in the presence and absence of EA and CD to explore the impact of the studied independent variables on entrapment efficiency (EE%) and % 6-G released after 24 h (Q24h). According to the desirability criteria, F8 (CD-functionalized transethoniosomal formula) was selected as the optimized formulation. F8 demonstrated higher EE%, permeation, deformability and stability than the corresponding TENs, ENs and NVs. Additionally, F8 showed higher cytotoxic and anti-inflammatory activity than pure 6-G. The synergism between complexation with CD and novel ultra-deformable nanovesicles (TENs) in the form of CD-TENs can be a promising drug delivery carrier for 6-G.

Applying pharmacokinetic/pharmacodynamic measurements for linezolid in critically ill patients: optimizing efficacy and reducing resistance occurrence.

PURPOSE: Linezolid (LZD) levels are frequently insufficient in intensive care unit (ICU) patients receiving standard dose, which is predictive of a poor prognosis. Alternative dosing regimens are suggested to address these insufficient levels, which are substantial factors contributing to the emergence of multidrug-resistant bacteria, resulting in increased morbidity and mortality among people who are critically ill. METHODS: Forty-eight patients admitted to the intensive care unit were enrolled in an open-label, prospective, randomized study and assigned to one of three LZD administration modes: intermittent groupI (GpI) (600 mg/12 h), continuous infusion groupII (GpII) (1200 mg/24 h) or continuous infusion with loading dose groupIII (GpIII) (on Day 1, 300 mg intravenously plus 900 mg continuous infusion, followed by 1200 mg/24 h on Day 2). We evaluated serum levels of LZD using a validated ultra-performance liquid chromatography (UPLC) technique. RESULTS: Time spent with a drug concentration more than 85% over the minimum inhibitory concentration (T > MIC) was substantially more common in GpII and III than in GpI (P < 0.01). AUC/MIC values greater than 80 were obtained more frequently with continuous infusion GpIII and GpII than with intermittent infusion GpI, at 62.5%, 37.5% and 25%, respectively (P < 0.01). In GpI, the mortality rate was significantly higher than in the other groups. CONCLUSION: In critically ill patients, continuous infusion with a loading dose (GpIII) is obviously superior to continuous infusion without a loading dose (GpII) or intermittent infusion (GpI) for infection therapy. Additionally, it might limit fluctuations in plasma concentrations, which may help overcome LZD resistance.

Applying Biopharmaceutical Classification System criteria to predict the potential effect of Cremophor® RH 40 on fexofenadine bioavailability at higher doses.

Aim: To study the impact of various permeability enhancers on fexofenadine bioavailability. Furthermore, to predict the potential effect of Cremophor® RH 40 on fexofenadine pharmacokinetics at higher doses using Biopharmaceutical Classification System criteria. Experimental methods: The effect of the dose increase (60-360 mg) on the dissolution and permeability behavior of fexofenadine-Cremophor RH 40 formulations was studied in humans. The Biopharmaceutical Classification System criteria of the drug was determined. Results & conclusion: Cremophor RH 40 improved the dissolution and bioavailability of fexofenadine. The pharmacokinetics increased linearly with the dose increase. Absorption number (An) was significantly increased after addition of Cremophor RH 40 in comparison to an unprocessed drug. Similar An values were observed throughout the same dose range. The dose number (D0) values were <1 whereas, all the dissolution number (Dn) values were >1 at the same dose level.

Effect of pineapple juice on the pharmacokinetics of celecoxib and montelukast in humans.

Aim: To study the influence of pineapple juice on the pharmacokinetics of celecoxib and montelukast in humans. Experimental methods: The research comprised two separate arms. Each arm was randomized, two-crossover periods separated by a 2-week washout period. Subjects received a single dose of celecoxib or montelukast after pretreatment with either water or pineapple juice for 4 days before the study beginning. Results & conclusion: Pineapple juice enhanced the systemic exposure of both drugs without any noticeable adverse effects. For celecoxib, Cmax and AUC0-∞ were increased significantly by 40 and 60%, respectively. Cl/F was decreased by 45% without affecting its t1/2. For montelukast, Cmax and AUC0-∞ were significantly increased by 21 and 48%, respectively, along with 25% decrease in clearance and 13% increase in t1/2.

Hydrogel-based matrices for controlled drug delivery of etamsylate: Prediction of in-vivo plasma profiles.

OBJECTIVES: To design oral controlled release (CR) hydrogel matrix tablets of etamsylate using various hydrophilic polymers. Additionally, to predict plasma concentration-time profiles of etamsylate released from different CR matrices. METHODS: Characterization of the in-vitro release rate was performed by various model dependent and model independent approaches. A simple numerical convolution strategy was adopted to predict the in-vivo performance of all matrices from their in-vitro percent released data. The statistical analysis was conducted utilizing a student t-test and ANOVA. RESULTS: The release of etamsylate from all matrices showed a deviation from Fickian transport mechanism except; F2 followed Case II release whereas, F9 and F11 obeyed Fickian diffusion. CR hydrogel based-matrices (F4 and F11) demonstrated the maximum drug retardation and satisfied the USP release limits. Concentration-time profiles of etamsylate were predicted successfully from the in-vitro release data of all prepared matrices. Pharmacokinetic parameters of etamsylate CR hydrogel matrices were significantly changed with comparison to reference product except F1. CONCLUSION: The designed (F2-F11) matrices had the capability to extend the plasma level of etamsylate for an adequate time. However, F4 and F11 were considered the most ideal formulations for once daily application of etamsylate. The prediction of in-vivo pharmacokinetics of etamsylate was very useful to assess the rationality of the designed matrices for the practical application in humans.

Simple HPLC Method for Quantitative Determination of Carbinoxamine in Human Plasma: Application in Pharmacokinetic Studies and Therapeutic Drug Monitoring.

A sensitive, specific and cost-effective HPLC method was developed for quantitative determination of carbinoxamine in human plasma using liquid chromatography with ultraviolet detection. A simple liquid-liquid extraction by ethyl acetate was used to extract carbinoxamine from human plasma. Satisfactory separation was achieved by a mobile phase consisting of 20 mM ammonium dihydrogen orthophosphate containing 0.01% triethyl amine (pH adjusted to 3 by using phosphoric acid) and acetonitrile in ratio of (75:25, v/v) at a flow rate of 0.9 mL/min on Hypersil® BDS C18 column (250×4.6 mm, 5 µm) column. The UV detector was set at 260 nm. The developed method was validated in human plasma with a lower limit of quantitation of 5 ng/mL for carbinoxamine. Linearity was demonstrated over the concentration range 5-200 ng/mL. The observed within- and between-day assay precision ranged from 1.902 to 14.90%; accuracy varied between 98.87 and 108.0%. This method can be used suitably for pharmacokinetic studies and in therapeutic drug monitoring in patients treated with carbinoxamine.