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Background. De Quervain's tenosynovitis is mucoid degeneration of the tendon sheaths of the two tendons that regulate the mobility of the thumb. As a result, the wrist's thumb side is painful and uncomfortable. Objectives. To assess radiofrequency's effectiveness in patients with de Quervain’s tenosynovitis. Design. A prospective randomized controlled trial. Setting. physical therapy department, Rail Way Hospital. Methods. 40 participants with de Quervain’s tenosynovitis. Participants were divided into two groups at random: group A (control group), which received an ultrasound, transverse friction massage, and strengthening exercises; and group B (study group), which received radiofrequency plus ultrasound, transverse friction massage, and strengthening exercises. Pain intensity, hand grip strength, and pinch strength were all measured at the baseline and after 4 weeks of treatment by using the visual analog scale, Jamar dynamometer, and pinch gauge, respectively. Results. All outcome indicators in both groups improved statistically significantly (P < 0.05), according to within-group comparisons. The between-group comparisons showed significant improvement in all outcome measures for both groups (P < 0.05), with the study group showing superior improvement to the control group; the study group's VAS improvement percentage was 28.7%, its grip strength improvement percentage was 6.71%, and its pinch strength improvement percentage was 28.6%. Conclusion. In comparison to ultrasound, transverse friction massage, and strengthen exercise, radiofrequency plus ultrasound, transverse friction massage, and strengthen exercise resulted in greater improvements in de Quervain's tenosynovitis patients' pain intensity, hand grip strength, and pinch strength.

Due to the wide applicability of separation techniques that rely on the property of differential migration in pharmaceutical formulations analysis, different analytical strategies have been proposed to resolve mixtures of multi-components pharmaceuticals. Three separation methods were developed and validated for the simultaneous determination of Paracetamol (PAR), Pseudoephedrine HCl (PSE) and Chlorpheniramine maleate (CHP). The first method is a thin-layer chromatographic (TLC) separation, followed by densitometric measurement. The separation was carried out on aluminium sheet of silica gel 60 F254 using ethanol:chloroform:ammonia (1:7:0.4, by volume) as the mobile phase. Determination of PAR, PSE and CHP was successfully applied over the concentration ranges of 3–25 µg/band, 0.5–10 µg/band and 0.1–6 µg/band, respectively. The second method is HPLC separation that was achieved on C18 column using the mobile phase acetonitrile:phosphate buffer pH 5 (10:90, v/v) at a flow rate 1 mL min−1. PAR, PSE and CHP were determined by HPLC in concentration ranges of 5–400 μg mL−1, 2–40 μg mL−1 and 0.5–16 μg mL−1, respectively. The third method is a capillary electrophoresis (CE) separation. The electrophoretic separation was achieved using 20 mM phosphate buffer (pH 6.5) at 20 kV. The linearity was reached over concentration ranges of 30–250 μg mL−1, 5–50 μg mL−1 and 0.8–20 μg mL−1 for PAR, PSE and CHP, respectively. The developed methods were validated with respect to linearity, precision, accuracy and system suitability. The proposed methods were successfully applied for bulk powder and dosage form analysis with RSD of precision

Objective: Pitavastatin calcium (PT) is an innovative drug of statins that enhances HDL-C and lowers LDL-C. However, myalgia has been reported in hyperlipidemic patients receiving statins. Therefore, co-administration of statins with NSAIDs such as Lornoxicam (LN) could be a solution to the former problem. Accordingly, this study aimed to formulate a bi-laminated oral disintegrating film (ODF) comprising PT in one layer and LN in the second one. Methods: For the formulation and optimization of PT-ODFs, a 31.21 full factorial design was carried out, where the impact of polymer type and concentration on disintegration time (DT) and % PT released after 10 min (Q10) was studied. PT-ODFs were prepared via the solvent casting method and then evaluated. One PT-ODF was chosen to represent the optimum formula according to the criteria of scoring the fastest DT and the highest Q10. The optimized PT-ODF was merged with the second film layer containing LN, forming a bi-laminated ODF named S1 that underwent an in vivo pharmacokinetic study compared to the commercially available tablets for PT (Lipidalon®) and LN (Lornoxicam®) using rats as an animal model. LC-MS/MS was used to analyze plasma drug concentrations. Results: All PT-ODFs showed acceptable outcomes. F1 scored the fastest DT (18.6±1.5 s) and the highest Q10 (91.3±3.0 %). S1 successfully recorded a maximum plasma concentration (Cmax) of 2.04 and 2.24 folds increase for PT and LN, correspondingly, compared to commercially available tablets. Conclusion: Merging PT and LN into bi-laminated ODF was promising for the fast delivery of both drugs with enhanced bioavailability.

Green analytical chemistry principles, as well as experimental design, are a combined approach adopted to develop sensitive reproducible stability indicating HPLC method for Zonisamide (ZNS) determination. The optimal conditions for three chromatographic parameters were determined using a central composite design of the response surface. Kromasil C18 column (150 mm × 4.6 mm, 5 µm) was utilized with ethanol, H2O (30:70 v/v) as a mobile phase at a flow rate of 1 mL/min at 35 °C. Good reproducibility and high sensitivity were achieved along (0.5–10 µg/mL) concentration range. In contrast, the TLC-densitometric method was performed on aluminum plates precoated with silica gel 60F254 as a stationary phase and chloroform: methanol: acetic acid (8:1.5:0.5 by volume) as a developing system. Reproducible results were obtained in the range of (2–10 μg/band). The chromatograms of HPLC and TLC were scanned at 280 nm and 240 nm, respectively. The suggested methods have been validated following ICH guidelines, and no statistically significant differences were detected between the results of the current study and the official USP method. It was also found that using experimental design implements the green concept by reducing the environmental impact. Finally, Eco-Scale, GAPI and AGREE were used to assess the environmental impacts of the suggested methods.

This work is dedicated to the greenness estimation of three proposed spectrophotometric techniques [e.g., ratio difference (RD), mean centering of ratio spectra (MCR) and continuous wavelet transform of ratio spectra (CWT)] for the determination of a binary combination named Ofloxacin (OFL) and Ornidazole (ORN). Applying the green analytical chemistry methods to assess the proposed methods has widely attained the analytical community care. The greenness assessment was performed via three evaluation approaches; the “Analytical Eco-Scale”, the “National Environmental Method Index” (NEMI) and “Green Analytical Procedure Index” (GAPI). Following the examination of the zero spectrum of OFL and ORN, it is observed that OFL and ORN spectra are overlapped, so they can be detected by the methods mentioned previously. The ratio difference method was carried out at wavelengths of 294.6 nm and 265.6 nm for OFL, 292 nm and 315 nm for ORN. The linear range was (2–15 µg/mL) for OFL and (3–30 µg/mL) for ORN. The MCR method based on the use of mean centered ratio spectra in dual steps and calculating the second ratio spectra mean centered values at 294.6 nm for OFL and 315 nm for ORN. The continuous wavelet transformation which carried out using MATLAB at wavelengths of 265 nm for OFL and 306 for ORN. These techniques were intended for the binary mixture analysis in bulk powder and pharmaceutical formulations with high recoveries. The developed methods were validated according to ICH guidelines. All techniques were statistically compared to either an official method for OFL or a reported method for ORN and the results indicate that there were not any significant differences.

The development and validation of the stability indicating HPLC technique has contributed to the understanding of the stability profile of ibuprofen (IBU) and phenylephrine (PHE). Stability profile was achieved for PHE, the drug was found to be liable to be influenced by stress oxidative conditions. Two oxidative degradates were formed and their structures were confirmed using IR and mass spectrometry. The drugs and degradation products were successfully separated using a a gradient elution method on YMC-C8 column with 0.1% hexanesulfonic acid and acetonitrile as solvents at pH 6.6. The flow rate was 1.0 mL.min− 1, and a diode array detector operating at 220 nm was used for UV detection. The proposed technique has been validated using ICH guidelines and its greenness was assessed according to Analytical Eco Scale metric.

Background: Thiazide diuretics are listed as one of the first-line antihypertensive treatment agents. Hydrochlorothiazide is mainly formulated with many antihypertensive agents as combined pill therapy. Objective: In this study, a new, simple, rapid and sensitive LC-MS/MS assay was developed, optimized and validated for the simultaneous quantification of commonly prescribed cardiovascular combined medications that are used for hypertension management, including Hydrochlorothiazide (HCT) in the presence of irbesartan (IRB), candesartan (CAN) and bisoprolol (BISO) in human plasma. Methods: RP-HPLC separation of analytes and internal standard (atorvastatin) was performed on Zorbax Eclipse XDB-C18 (4.6×50 mm 5-Micron) using acetonitrile: (0.05%) formic acid (80:20), as an eluting system with a run time of less than 5.0 min. Results: Validation was carried out according to FDA guidelines for bioanalytical method. The recoveries were higher than 84.30%, the accuracy was within 86.82–110.17 % and the RSD was below 10% for all the studied compounds. Conclusions: The suggested method is highly appropriate for routine assays of the studied combination therapy in view of the lower LLOQ, simple extraction process, and short run time. The method can be further investigated and used for pharmacokinetics studies of the studied different antihypertensive combinations.

Background Modafinil (MDF) is one of the drugs used for the treatment of narcolepsy. Objective This manuscript describes the development and validation of two chromatographic stability-indicating methods for MDF in the presence of its acid-induced degradation product. Methods MDF was degraded under different stress conditions and identification of the degradation product was performed using IR and mass spectroscopy. The first method involved TLC, in which plates precoated with silica gel G60 F254 were used and the developing system was dichloromethane– methanol (9:1, v/v). The second method was an eco-friendly (HPLC) method that utilized a C-18 column and ethanol–H2O (30:70, v/v) as a mobile phase with a flow rate of 1 mL/min and UV detection at 220 nm. Results Good linear relationships were obtained within the ranges 1–10 µg/band and 2–10 µg/mL for TLC–densitometry and HPLC, respectively. The obtained results were statistically compared with those of the official HPLC method and showed no significant difference with respect to their accuracy and precision at P = 0.05. Greenness scores represent excellent green analysis results in comparison with the reported studies. Conclusions The proposed methods were validated according to ICH guidelines and were applied on bulk powder and pharmaceutical dosage forms using eco-friendly mobile phases in line with worldwide trends. Highlights Chromatographic methods have been validated for the estimation of MDF in the presence of its degradation product. Clarification of the degradation pathway and elucidation of the structure were stated for the first time. This is the first published method using greenness assessment metrics for the analysis of MDF.

Introduction While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past. Areas covered Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late 'big bang' of domain combinations. Expert opinion Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.

Aim: Helicobacter pylori infection is a prevalent global bacterial infection that can potentially exaggerate symptoms of other serious infections like SARS-CoV-2 (COVID-19). Methodology: Herein, an efficient, accurate and cost-effective high-performance liquid chromatography-diode array detector method was developed and validated for determination of the novel triple therapy combination of tinidazole (TD), clarithromycin (CLR) and lansoprazole (LAN) in different analytical matrices (pharmaceutical formulation, dissolution media and spiked human plasma). Results: Successful chromatographic separation was achieved using Agilent Microsorb-MV 100–5 CN column (250 × 4.6 mm, 5 μm) and a mobile phase consisted of acetonitrile and 10.0 mM phosphate buffer, pH 7.5 ± 0.1 at flow rate of 1 ml/min via gradient elution. UV-detection was accomplished at 210.0 nm for CLR and 290.0 nm for TD and LAN. Conclusion: The developed method clearly provides a reliable, beneficial and cost-effective tool for quality control, dissolution testing and biological applications of the mentioned drugs.

Nowadays, Green Analytical Chemistry is widely applied to provide various analytical methods with eco-friendly procedures employing the least toxic, harmful reagents on humans and the environment without affecting the efficacy of the determination. Accordingly, two eco-friendly, accurate, and reliable high-performance thin-layer chromatography-densitometry and high-performance liquid chromatographic methods were established for the determination and separation of two antispasmodic drugs, namely phloroglucinol and trimethylphloroglucinol in their pure, combined dosage form along with phloroglucinol toxic impurity, 3,5-dichloroaniline. For high-performance thin-layer chromatography-densitometry, efficient separation was developed via utilizing the stationary phase of high-performance thin-layer chromatography silica gel 60 F

Objectives: Baclofen is a skeletal muscle relaxant with an anti-inflammatory effect. The current market products of baclofen are oral tablets and intrathecal injection which cause many undesirable systemic side effects. This study aimed to formulate topical formula of baclofen to decrease systemic side effects. Topical drug delivery systems formulated as nanoparticles (NPs) enhanced the low drug release and the low bioavailability of the traditional gels. This occurs by prolonging the contact time and increasing the permeability of the drug through the skin. Methods: In this study, formulae of the baclofen-loaded Eudragit® RL100 (ERL) NPs were prepared by nanoprecipitation method. Polyvinyl alcohol (PVA) was added as a stabilizer. The NPs were characterized by measuring their particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency percent (EE %) values. Their spherical morphology was confirmed using transmission electron microscopy (TEM). Viscosity was also measured. In vitro release and permeation studies were done to evaluate the release of the drug from the NPs gel and the permeability of the drug through the skin. The results were compared with formulated baclofen traditional gel. Results: ERL concentrationand organic phase ratio were the main factors affecting the NPs formulation. A decrease in the particle size was observed with an increase in ERL% while the smallest particle size was observed with formulae containing organic phase (acetone: methanol) in the ratio of 1: 3. The highest EE% was observed with the highest ERL concentration and the same organic phase ratio (acetone: methanol 1:3). Formulae B3, B6, B9 were selected for their most promising results. Their particle size was 187.4 ±2.81, 126.3 ±1.47, 120.0 ±1.06 nm and their EE% was 78.9 ±0.30, 83.3 ±0.26, and 86.6 ±1.12, respectively. The percentages of the drug released from the selected formulae as well as the percentage of the permeated drug were significantly higher than that of the baclofen traditional gel. Conclusion: ERL NPs were capable of releasing baclofen and improving its permeability through the skin so it may be considered as a suitable promising alternative drug delivery system.

Hepatic encephalopathy (HE) is a debilitating and life-threatening disease. Results from acute or chronic liver failure and is characterized by abnormal cerebral and neurological alterations. This study aimed at investigating the effect of allicin, the major functional component in freshly crushed garlic extract, on thioacetamide (TAA)-induced HE in rats. Induction of HE by a single dose of TAA (300 mg/kg; I.P.) was associated with a marked elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, total protein, blood urea nitrogen and serum ammonia besides reduction in the serum level of albumin. Moreover, it was accompanied with an increase in the hepatic and brain levels of inflammatory mediators; TNF-α and IL-1β as well as elevation of the hepatic and brain levels of oxidative stress biomarkers; reduced glutathione and lipid peroxidation evidenced by malondialdeyde. Oral administration of allicin (50, 100 and 200 mg/kg; P.O.) for 6 days prior to TAA injection restored the serum liver function, hepatic and brain levels of inflammatory mediators as well as oxidative stress biomarkers in a dose-dependent manner. From our results, it can be concluded that allicin has a protective effect on TAA-induced HE in rats in a dose-dependent manner due to its powerful antioxidant and anti-inflammatory properties.

Residues of veterinary drugs in poultry meat have serious health effects on humans (e.g., antimicrobial resistance, carcinogenicity, and hypersensitivity), which make the control of veterinary drug residues an important parameter in ensuring consumer protection. This work was performed to quantitatively determine two co-formulated anti-infective veterinary agents, tylosin tartrate (TYT) and doxycycline hydrochloride (DOX) in different tissues of broiler chickens (liver, muscles, and fat) using high performance liquid chromatography. The chicken was treated with the recommended dose of a binary mixture of the drugs (Tydovet). Moreover, the study aimed to estimate the withdrawal time of both drugs in chicken tissues. The analysis was done by solvent extraction and solid-phase extraction for clean-up of samples from the tissue matrix, followed by liquid chromatographic determination of the cited drugs with UV-detection. Residue decline with time was tracked, and both antibiotics were found to be more persistent in liver tissues than other tissues (muscle and fat). The effect of freezing and cooking was investigated on tissue residue levels. While freezing had little effect on the concentration of both antibiotics; cooking, as anticipated, led to a marked decline. Therefore, it is recommended to pay attention to the proper withdrawal periods before marketing to ensure the hygienic suitability of broilers edibles for safe human consumption. PRACTICAL APPLICATION: This novel study measures tylosin and doxycycline residues simultaneously in different tissues (muscle, fat, and liver) after administration of Tydovet powder to the broiler chicken. Residues in fat persisted for a longer time than in muscle in case of TYT, whereas the reverse was noticed in DOX.

While the origin and early evolution of proteins and their biosynthetic mechanisms remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Here we describe how chronologies and networks provide a window into the past and untangle the emergence of proteins, the development of the biosynthetic apparatus, and a language behind translation and ribosomal growth.

Modafinil (MDF) is one of the neurostimulants with a potential effect in the COVID-19 ICU ventilated patients and post-COVID neurological syndrome treatment. Four rapid, simple and cost-effective stability indicating spectrophotometric methods were used for estimation of MDF in the presence of its acidic degradation product, namely; ratio difference (RD), first derivative of the ratio spectra (1DD), mean centering (MCR) and ratio subtraction method (RS). These methods were validated according to ICH guidelines and all methods revealed a good linearity in concentration range of (5-30 µg/mL) in addition to a good accuracy and precision with mean percentage recovery of 99.97 ± 0.305 for (RD), 100.10 ± 0.560 for (1DD), 100.02 ± 0.483 for (MCR) & 99.18 ± 1.145 for (RS) method. Specificity of the proposed methods was assessed and MDF was determined in the presence of up to 80% of its acidic degradation product for RD, 1DD, MCR and RS methods. The proposed methods were successfully applied for the determination of MDF in bulk powder and its tablet dosage form with mean percentage recovery of 100.33 ± 0.915 for (RD), 100.62 ± 0.985 for (1DD), 99.70 ± 0.379 for (MCR) and 100.21 ± 0.313 for (RS) method. The results obtained were statistically compared with those of official HPLC method and showed no significant difference with relevance accuracy and precision.

Mentha species are medicinally used worldwide and remain attractive for research due to the diversity of their phytoconstituents and large therapeutic indices for various ailments. This study used the metabolomics examination of five Mentha species (M. suaveolens, M. sylvestris, M. piperita, M. longifolia, and M. viridis) to justify their cytotoxicity and their anti-Helicobacter effects. The activities of species were correlated with their phytochemical profiles by orthogonal partial least square discriminant analysis (OPLS-DA). Tentatively characterized phytoconstituents using liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) included 49 compounds: 14 flavonoids, 10 caffeic acid esters, 7 phenolic acids, and other constituents. M. piperita showed the highest cytotoxicity to HepG2 (human hepatoma), MCF-7 (human breast adenocarcinoma), and CACO2 (human colon adenocarcinoma) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. OPLS-DA and dereplication studies predicted that the cytotoxic activity was related to benzyl glucopyranoside-sulfate, a lignin glycoside. Furthermore, M. viridis was effective in suppressing the growth of Helicobacter pylori at a concentration of 50 mg mL−1. OPLS-DA predicted that this activity was related to a dihydroxytrimethoxyflavone. M. viridis extract was formulated with Pluronic® F127 to develop polymeric micelles as a nanocarrier that enhanced the anti-Helicobacter activity of the extract and provided minimum inhibitory concentrations and minimum bactericidal concentrations of 6.5 and 50 mg mL−1, respectively. This activity was also correlated to tentatively identified constituents, including rosmarinic acid, catechins, carvone, and piperitone oxide.

Thin layer chromatography (TLC) is a powerful and simple technique for screening and quantifying low quality and counterfeit pharmaceutical products. The detection methods used to detect and quantify separate analytes in TLC ranges from the densitometric method to mass spectrometric or Raman spectroscopic methods. This work describes the development and optimization of a simple and sensitive TLC method utilizing a smartphone CCD camera for verification of both identity and quantity of antibiotics in dosage form, namely ofloxacin and ornidazole. Mixtures of ofloxacin and ornidazole were chromatographed on a silica gel 60 F254 plate as a stationary phase. The optimized mobile phase is n-butanol : methanol : ammonia (8 : 1 : 1.5 by volume). Iodine vapor has been used as a “universal stain” to visualize the spots on the TLC plates in order to obtain a visual image using the smartphone camera and a desk lamp as an illumination source, thus eliminating the need for a UV illumination source. The recorded images were processed to calculate the Rf values (Rf values for ofloxacin and ornidazole were 0.12 and 0.76, respectively) which provide identity of the drugs while spot intensity was calculated using a commercially available smartphone app and employed for quantitative analysis of the antibiotics and “acetaminophen” as an example of a counterfeit substance. The smartphone TLC method yielded a linearity of ofloxacin and ornidazole in the range of 12.5–62.5 μg/band and 500–1000 μg/band, respectively. The limit of detection was found to be 1.6 μg/spot for ofloxacin and 97.8 μg/spot for ornidazole. The proposed method was compared with the bench top densitometric method for verification using a Camag TLC Scanner 3, the spot areas were scanned at 320 nm. The Rf value of ofloxacin and ornidazole was calculated to be 0.12 and 0.76, respectively. The densitometric method yielded a linearity of ofloxacin and ornidazole in the range of 5–40 μg/band and 5–50 μg/band, respectively. The limit of detection was found to be 0.8 μg/spot for ofloxacin and 1.1 μg/spot for ornidazole. The proposed method has been successfully applied for the determination of ofloxacin and ornidazole present in more than one pharmaceutical dosage form and was comparable to the densitometric method.

Background It has been reported that Moringa oleifera (MO) has different medicinal properties. The aim of this study was to evaluate the hepatoprotective role of Moringa oleifera extract on acetaminophen-induced liver fibrosis in albino rats on a biochemical and histological basis. Forty male albino rats were divided into four groups: group I (control group), healthy rates; group II (acetaminophen group), rates received acetaminophen for induction of liver fibrosis; group III (treated group), liver fibrosis of rates treated with Moringa oleifera extract; and group IV (prophylactic group), rates treated with Moringa oleifera extract before and after induction of liver fibrosis. Serum liver function parameters were quantified using a spectrophotometer, while tumor necrosis factor α (TNF-α) and transformed growth factor beta (TGF- β) in liver tissue homogenate by means of enzyme-linked immunosorbent assay (ELISA), and expression of liver tissue TNF-α and TGF-genes was measured by real-time PCR after extraction and purification. Hepatic tissue was also evaluated under a microscope for histopathological changes. Results Our results showed a significant decrease in liver enzymes, TNF-α, and TGF-β in the treated and prophylactic groups compared to the acetaminophen group, and our biochemical data were consistent with the histopathological findings confirming the hepatoprotective effect of Moringa oleifera extract. Conclusions Biochemical parameters and histopathology results provide evidence that Moringa oleifera ethanolic extract has a great potential to prevent and improve liver damage due to its protective activity.

Rosuvastatin calcium (RSC) is a statin which, in addition to its anti-hypercholesteremic effects, was found to have a potential anticancer activity. The target of the present study is to develop self nano-emulsifying drug delivery systems (SNEDDS) loaded with RSC to overcome its poor solubility, and augment its anticancer activity. A combined mixture-process experimental design was chosen for the optimization of SNEDDS by changing its mixture and process components, where the mixture components were the percentage of Smixture (surfactant and co-surfactant) (X1) and the percentage of oil (X2). The process components were the ratio of surfactant to co-surfactant (X3), and the type of surfactant (X4). Twenty-four formulae were evaluated for % transmittance and saturated solubility. The optimized formula (O1) was selected based on the highest % transmittance and highest drug solubility, where the % transmittance was 99.05 ± 0.09% and the saturated solubility was 80.52 ± 2.57 mg/ml. The optimized formula has a globule size of 17.53 ± 0.89 nm, a zeta potential of − 10.2 ± 0.21 mV, and a cloud point of 88.5 ± 0.54 °C. Transmission electron microscopy demonstrated spherical droplet morphology. In vitro drug release showed remarkable increase in the drug release from the optimized formula as compared to the corresponding standard RSC. The anticancer activity of O1 was evaluated in HepG2 cell-line, where the IC50 value was 16.2 ± 0.23 μg/ml. The optimized formula increased cell death by both apoptosis and necrosis. Our results show that the optimized SNEDDS formula is promising for enhancing the anticancer effect of RSC.

Skin health is vital for a healthy body. Herbal remedies have long been used for skin care, and their global use has tremendously increased over the past three decades. Although cellulite is seen as a normal condition by the medical community, it is considered a serious cosmetic concern for most affected women. Many topical anti-cellulite creams are available on the market, but unfortunately, their efficacy has not been proven scientifically. Microneedles (MNs) represent a new approach to enhance the permeation of loaded medication through the skin. In this study, the anti-cellulite effects of Vitex agnus-castus and Tamarindus indica extracts were compared using safe and effective polymeric MNs. This delivery system offers a painless alternative to the combined treatment strategy of microneedling devices and anti-cellulite products. The selected standardized extracts were evaluated for their mineral, phenolic and flavonoid contents, which are correlated to a promising antioxidant effect, as demonstrated by an in vitro radical scavenging activity assay. 3D-printing techniques were chosen for fabrication of a micromold, which is inexpensive for mass production. To ensure that MNs were sufficiently strong to perforate the skin without breaking, axial failure force was measured using a micro-mechanical test machine. The anticellulite effects of MNs were assessed using an in vivo diet-induced obesity guinea pig model. Skin properties, histopathology and inflammatory markers were examined. MNs loaded with plant extracts were statistically comparable in normalizing the oxidative state and reducing inflammation, while myeloperoxidase levels were more significantly reduced by T. indica than by V. agnus-castus. This novel delivery system opens the door for new transdermal strategies for cellulite management.

Multilocus sequence typing (MLST) was used to study the genetic diversity and population structure of 48

Background Irritable bowel syndrome (IBS) is a common disorder leading to undesirable pain. Phloroglucinol (PHG) and trimethylphloroglucinol (TMG) are co-formulated as spasmolytic medication that is considered to be effective in reducing smooth muscle spasm. 3,5-Dichloroaniline (DCL) is a specified PHG pharmacopoeial impurity which needs to be monitored to avoid its toxic effects. Objective Different smart approaches are presented to provide simple, reliable, and economic spectrophotometric methods able to resolve the severe overlap in the spectra of PHG and TMG in their pure and pharmaceutical forms, in addition to their estimation in the presence of DCL as a toxic impurity of PHG without any need for initial separation. Methods The presented work includes univariate methods, derivative ratio (DR), ratio difference (RD), mean centering (MCR) and deconvulated Fourier method (DF), which were able to determine PHG and TMG simultaneously in their binary mixture. Firstly, DCL was estimated in the zero order, where the two drugs have zero absorption at 247.0 nm, and then its contribution was eliminated by applying ratio subtraction method. Multivariate chemometric partial least squares (PLS) and principal component regression (PCR) models were also applied to determine PHG and TMG simultaneously in the presence of the impurity, DCL Results Univariate methods were applied in the range 5.0–30.0, 2.5–25.0, and 1.0–12.0 µg/mL for PHG, TMG, and DCL, respectively. The proposed chemometric models were used in the range 6.0–14.0, 5.0–25.0 and 2.0–10.0 µg/mL for PHG, TMG, and DCL, respectively. These analytical approaches succeeded in estimating the cited drugs in their pharmaceutical formulation and assessing content uniformity of dosage units. The methods were statistically compared with a reported HPLC method, and the results revealed no significance statistical difference. Conclusion This work provides for the first time successful univariate and multivariate PLS and PCR methods to assess PHG and TMG in the presence of DCL as a toxic impurity along with content uniformity testing of dosage units. Highlights Comparative univariate and multivariate spectrophotometric analytical approaches are presented, for the first time, for estimation of spasmolytic formulation of PHG and TMG in the presence of DCL as a PHG toxic impurity. Successful application to content uniformity testing of Stopspasm® dosage form is demonstrated. A statistical study, including t-tests and one-way analysis of variance (ANOVA), was conducted.

Impaired memory and cognitive function are the main features of Alzheimer’s disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood–brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 23-factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (−42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension.

Solid contact ion-selective electrodes (SC-ISEs) have created a new, promising field in pharmaceutical and biological analysis, recognized as an energy-saving, straightforward, and environmentally friendly technique. Hence, in the present study, miniaturized solid-contact ion-selective sensors have been fabricated as well as designed for the simultaneous in-line quantification of cationic amlodipine (AML) and anionic valsartan (VAL) in binary and ternary mixtures with hydrochlorothiazide (HCT). A screen-printed carbon electrode and a PVC polymer ion sensing membrane are the essential core of the suggested sensors. A conductive polymer interlayer of polypyrrole (PPy) was utilized as an ion-to-electron transducer embedded between the carbon electrode and the polymer ion sensing membrane. The influence of PPy resulted in a reduction of potential drift to μV/h and enhanced electrode stability. The performance of the suggested sensors was evaluated in accordance with IUPAC guidelines. The sensors proposed for both drugs presented stable, linear, as well as rapid responses over wide AML and VAL concentration ranges (3.0 × 10−6 to 1.0 × 10−3 M and 1.0 × 10−5 to 1.0 × 10−3 M, respectively). The fabricated potentiometric sensors were also implemented to determine the studied drugs in spiked human plasma without requiring any sample pre-treatment or derivatization. Additionally, the investigated method was also thoroughly evaluated for its greenness using a variety of green metrics.