Non-steroidal Anti-inflammatory Drugs Diclofenac Sodium Research Articles

Circulating miR-222-3p is associated with ankylosing spondylitis development and predicts therapeutic efficacy of nonsteroidal anti-inflammatory drugs.

Ankylosing spondylitis (AS) is a chronic rheumatic disease, and some microRNAs (miRNAs) in AS have been identified. This study aimed to measure miR-222-3p expression in AS patients, investigate the association of miR-222-3p with AS disease activity, and explore the clinical value of miR-222-3p in diagnosing AS and predicting therapeutic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on AS patients. This study included 96 patients with AS, 58 patients with rheumatoid arthritis (RA), and 90 healthy controls. miR-222-3p expression was detected by reverse-transcription quantitative polymerase chain reaction (PCR). The ability of miR-222-3p to discriminate between different groups was evaluated by receiver operating characteristic analysis. The predictive value of miR-222-3p on the efficacy of NSAID treatment for AS was assessed by logistic regression analysis. AS patients treated with oral NSAIDs diclofenac sodium were divided into response (n = 76) and no-response (n = 20) groups after 16 weeks of treatment. miR-222-3p in AS patients was higher than that in healthy subjects and RA patients. miR-222-3p had high diagnostic value in distinguishing patients with AS from RA patients and healthy controls. miR-222-3p, increased in active AS patients, had the ability to screen active AS patients from inactive AS patients. miR-222-3p was decreased in the response group, and had high accuracy in predicting the therapeutic efficiency of NSAIDs. The findings indicate that increased miR-222-3p in AS patients may function as a diagnostic biomarker for AS, and predictive biomarker for the therapeutic efficacy of NSAIDs in patients with AS. In addition, miR-222-3p is associated with AS disease activity.

Systemically Acting Diclofenac Sodium Patch for Control of Low Back Pain: A Randomized, Double-Blind, Placebo-Controlled Study in Japan.

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used for pain disorders such as low back pain and exist in multiple formulations; however, no systemically acting transdermal formulations are available for low back pain. Transdermal formulations can be safely administered even to patients with trouble swallowing or at risk of aspiration, and without regard to the effect of food on drug absorption. Unlike locally acting formulations, systemically acting transdermal formulations need not be applied at the target site, so dosing is simple and the burden is not on one area of the skin. A patch with the systemically acting NSAID diclofenac sodium is approved in Japan for treatment of cancer-related pain, and we hypothesized that it would be useful for controlling low back pain. This randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of diclofenac sodium patch in Japanese patients with low back pain. Eligible patients were randomized to receive diclofenac sodium patch 75mg or 150mg or placebo once daily for 2weeks. The primary endpoint was pain intensity assessed on a visual analog scale (VAS). Primary analysis of the primary endpoint showed that both doses of the diclofenac sodium patch (150mg and 75mg) were superior to placebo in terms of absolute change from baseline in mean 3-day VAS score after 2weeks' treatment; the mean difference between the active and placebo treatments in this variable was -5.67 [95% confidence interval (CI) -9.34 to -2.00] mm in the 150mg group and -5.68 (95% CI -9.34 to -2.01) mm in the 75mg group. Most adverse events were mild. No serious adverse events occurred. In Japanese patients, diclofenac sodium patch is effective for the relief of low back pain and is well tolerated. JPRN number, JPRN-JapicCTI-205134.

Transplantation of adipose-derived mesenchymal stem cells ameliorates acute hepatic injury caused by nonsteroidal anti-inflammatory drug diclofenac sodium in female rats

BackgroundAlthough the beneficial role of adipose-derived mesenchymal stem cells (AD-MSCs) in acute liver injury has been addressed by numerous studies employing different liver injury inducers, the role of rat AD-MSCs (rAD-MSCs) in diclofenac sodium (DIC) – induced acute liver injury has not yet been clarified. ObjectiveThis study aimed to investigate whether rat adipose- rAD-MSCs injected intraperitoneal could restore the DIC-induced hepatoxicity. MethodsHepatotoxicity was induced by DIC in a dose-based manner, after which intraperitoneal injection of rAD-MSCs was performed. ResultsHere, the transplanted cells migrated to the injured liver, and this was evidenced by detecting the specific SRY in the liver samples. After administering DIC, a significant decrease in body weight, survival rate, serum proteins, antioxidants, anti-apoptotic gene expression, and certain growth factors, whereas hepatic-specific markers, pro-inflammatory mediators, and oxidative, pro-apoptotic, and ER-stress markers were elevated. These adverse effects were significantly recovered after engraftment with rAD-MSCs. This was evidenced by enhanced survival and body weight, improved globulin and albumin values, increased expression of SOD, GPx, BCL-2, VEGF, and FGF-basic expression, and decreased serum ALT, AST, ALP, and total bilirubin. rAD-MSCs also reduced liver cell damage by suppressing the expression of MDA, IL-1B, IL-6, BAX, JNK, GRP78/BiP, CHOP, XBP-1, and cleaved caspase 3/7. Degenerative hepatic changes and multifocal areas of fatty change within liver cells were observed in DIC-received groups. These changes were improved with the transplantation of rAD-MSCs. ConclusionsWe could conclude that targeted AD-MSCs could be applied to reduce hepatic toxicity caused by NSAIDs (DIC).

Reversal of itraconazole resistance in Sporothrix brasiliensis and Sporothrix schenckii by nonsteroidal anti-inflammatory drugs

BackgroundThe emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon. AimsThis study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii. MethodsMinimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method. ResultsWhen used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively. ConclusionsThe results indicate that the combination of itraconazole and the evaluated NSAIDs are a promising strategy for the treatment of sporotrichosis.

CHARACTERISTICS OF THE MECHANISMS OF CYTOPROTECTIVE ACTIVITY OF CRYOPRESERVED PLACENTA EXTRACT ACCORDING TO MORPHOLOGICAL AND BIOCHEMICAL STUDIES OF THE GASTRIC MUCOSA IN THE EXPERIMENT

Relevance. Non-steroidal anti-inflammatory drugs (NSAIDs) are used as antipyretics and analgesics. In this case, NSAIDs have a side effect - ulcerogenic. Therefore, it is important to find means to correct the ulcerogenic action of NSAIDs. Potential antiulcerogenic action may be in cryopreserved human placenta extract "Cryocell-placental cryoextract".
 Objective: to investigate the effect of cryopreserved placenta (CEP) extract on the morphological state of the stomach and the processes of protein synthesis in the gastric mucosa with the introduction of NSAIDs diclofenac sodium in rats with experimental rheumatoid arthritis.
 Materials and methods. The study was performed on 28 nonlinear male rats weighing 200-220 g. The animals were divided into 4 groups: I (n = 7) – intact rats; II (n = 7) – rats with adjuvant arthritis (AA), this is a treatment without treatment; III (n = 7) – rats with AA, treated with diclofenac sodium (DN), 8.0 mg / kg, intragastrically (i/g); IV (n = 7) – rats with AA, treated with DN, 8.0 mg / kg, i/g and CEP, 0.16 ml / kg body weight, intramuscularly (i/m).
 AA was simulated by subplantar injection of complete Freund's adjuvant into the hind right limb at a rate of 0.1 ml per rat. The day of adjuvant administration was considered as the "0" day of the experiment. AA treatment was performed from 14 to 28 days. DN was applied daily, and CEP – with an interval of 3 days: for 14, 17, 20, 23 and 26 days. On day 28, the animals were removed from the experiment by cervical dislocation under inhalation anesthesia.
 To assess morphological changes, gastric fragments were fixed in 10.0% neutral formalin solution. Histological sections 5–7 μm thick were stained with hematoxylin and eosin, as well as Schiff's reagent (fuchsin sulfuric acid) with iodic acid. The concentration of total protein (TP) was determined spectrophotometrically by light absorption at a wavelength of 546 nm. The content of RNA and DNA in the homogenates of the gastric mucosa was determined spectrophotometrically by reaction with perchloric acid.
 Results. In rats with AA, the mucous membrane (MM) had a preserved structure in all animals. There were no signs of hyper- or hyposecretion of mucins when stained with a chic reaction with alcyan blue. There were foci of desquamation of the superficial epithelium and single lymphocytes. The introduction of DN in rats with AA led to signs of erosive changes in MM. Deep erosions and single ulcerative defects were found in 28.6% of rats, reaching the depth of the lesion to the muscle plate. There is a small amount of mucopolysaccharides with a predominance of acidic glycoproteins. Reduced content of neutral glycoproteins. Single desquamated epitheliocytes were detected. Focal lympho-plasmacytic infiltration with exudate with eosinophilic leukocytes was noted in the submucosal layer of MM. Against the background of the combined use of DN and CEP in rats with AA in any animal, no significant violations of the histoarchitectonics of the MM, except for isolated foci of desquamation of the superficial epithelium.
 In gastric MM homogenates in rats with AA there was a decrease (p <0.01) in the level of TP by 14.1% and a decrease (p <0.05) in the content of RNA and DNA by 27.5% and 14.3%, respectively, relative to indicators of intact animals.
 Against the background of DN monotherapy, there was an even greater decrease (p <0.001) in the level of TP: by 26.2% (40.3 ± 1.43 μg / mg) relative to intact animals (54.6 ± 1.39 μg / mg). And the content of RNA and DNA was 0.59 ± 0.57 μg / ml and 2.21 ± 0.27 μg / ml, respectively.
 Against the background of the combined use of DN and CEP, comparable to the level of intact animals indicators of TP and DNA were noted. Thus, the level of TP was 53.0 ± 2.09 μg / mg, which was only 2.9% lower than intact animals (54.6 ± 1.39 μg / mg), and the DNA content by 5.1% (p = 0.3) was lower than intact animals (3.1 ± 0.12 μg / ml) and was respectively 2.94 ± 0.08 RNA level (1.72 ± 0.12 μg / ml) on 17.6% exceeded (p = 0.1) intact animals (1.46 ± 0.08 μg / ml).
 Conclusions. The combined use of placental cryoextract and diclofenac sodium eliminates the negative effect of the latter on protein metabolism in the gastric mucosa of rats with adjuvant arthritis. Thus, the level of total protein was 53.0 ± 2.09 μg / mg, which is only 2.9% lower than intact animals. Restoration of diclofenac sodium-induced mucin secretion by the integumentary epithelium of the gastric mucosa is one of the mechanisms of cytoprotective activity of cryopreserved placenta extract in experimental ulcerogenesis.

High adsorption of sodium diclofenac on post-synthetic modified zirconium-based metal-organic frameworks: Experimental and theoretical studies

Water pollution by pharmaceuticals is currently a great concern due to their ecological risks. In this study, zirconium-based metal–organic frameworks (UiO-66-(COOH)2) were used for removal of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac sodium (DCF). They have been synthesized using a hydrothermal method. Copper and iron metal ions were incorporated in the framework using post-synthetic modification techniques to produce UiO-66-(COOCu)2 and UiO-66-(COOFe)2. The resulted MOFs were characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning/transmission electron microscopy, and Brunauer–Emmett–Teller. The effects of the pH, initial concentration, and adsorption time on the adsorption process of diclofenac were studied. The maximum adsorption capacities obtained on UiO-66-(COOH)2, UiO-66-(COOCu)2, and UiO-66-(COOFe)2 were 480.5, 624.3, and 769.1 mg/g, respectively. The adsorption of diclofenac was found to be better fitted with Langmuir isotherm and pseudo-second-order kinetic models. The adsorption mechanism was investigated using XRD, FT-IR, density functional theory and Monte Carlo simulation, in which the latter method was used to calculate the adsorption energies and determine the possible interactions between diclofenac and the adsorbents. UiO-66-(COOH)2, UiO-66-(COOCu)2, and UiO-66-(COOFe)2 exhibited good recyclability for diclofenac removal, which confirms the sustainability of these materials.

Anti-arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X-ray microtomographic and histopathological analysis).

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Bioactive peptides and peptide‐rich protein hydrolyzate represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant (modified Mycobacterium butyricum) in rats. The antiarthritic effect of CETH was studied on the 28th day of the experiment after 2 weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X‐ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non‐steroidal anti‐inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose‐dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammation, inhibition of osteolysis, reduction in the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents for the first time that CETH may be a powerful potential nutraceutical agent or bioactive component in the treatment of rheumatoid arthritis.

HSA nanoparticles in drug recognition: mechanistic insights with naproxen, diclofenac and methimazole

Protein-based nanoparticles offer a suitable targeted delivery platform to drugs in terms of biocompatibility, biodegradability and abundance in nature. Physicochemical understanding of drug encapsulation by protein nanoparticles and their impact on protein aggregation is essential. In this work, we have examined quantitative aspects of encapsulation of non-steroidal anti-inflammatory drugs naproxen and diclofenac sodium, and anti-thyroid drug methimazole in nanoparticles of human serum albumin (HSA NPs) by using ultrasensitive calorimetry. Thermodynamic signatures accompanying the interactions revealed that the partitioning of all these drugs in HSA NPs is primarily driven via contributions from desolvation of highly hydrated nanoparticles surface. Furthermore, the effect of these nanoparticles on fibrillation of HSA has also been studied. HSA NPs are determined to be ineffective towards inhibition of fibrillation under employed conditions. However, the extent of inhibition by HSA NPs varies depending upon the structural characteristics of the drugs. Such studies help to gain mechanistic aspects on drug loading into protein-based nanoparticles and are expected to provide useful insights into improving existing nano-drug carriers and their efficiency in preventing protein fibrillation. Communicated by Ramaswamy H. Sarma

Elucidation of the effect of concomitant administration of Metformin and Diclofenac Sodium on insulin resistance, pro-inflammatory cytokines and oxidative stress markers in in vivo models

Prevalence of chronic disorders like arthritis is frequently observed in diabetic patients, especially among the geriatric population. To combat such a situation, non-steroidal anti-inflammatory drugs (NSAIDs) are mostly co-prescribed along with antidiabetics. Thus present study tried to evaluate the safety and efficacy of concomitant use of drugs in animals induced with comorbid conditions. Diabetes and chronic inflammation were induced in rats by Streptozotocin and Nicotinamide and Freund’s Complete Adjuvant respectively. These medical conditions were treated with antidiabetic Metformin and NSAID Diclofenac Sodium for 28 days. Blood glucose, paw edema were recorded weekly. At the end of the study duration, Insulin, C-peptide, cytokines in serum, oxidative stress biomarkers in liver and kidney tissues were estimated. Concomitant therapy of Metformin and Diclofenac Sodium was successful in reducing the glucose level and inflammation parameters. However, reduction by 30.06% and 46.51% in insulin and C-peptide levels respectively were evident in the rats treated with concomitant medications as compared to the normal. Concomitant therapy also failed to restore the normal levels of the pro-inflammatory cytokines. Perturbation was also evident in the antioxidant status of the tissues. Results from this study can thus be utilized to optimize the therapeutic regimen of patients to ensure safe medication.

Thermosensitive Drug Delivery System SBA-15-PEI for Controlled Release of Nonsteroidal Anti-Inflammatory Drug Diclofenac Sodium Salt: A Comparative Study.

Mesoporous SBA-15 silica material was prepared by the sol–gel method and functionalized with thermosensitive polyethylenimine polymers with different molecular weight (g·mol−1): 800 (SBA-15(C)-800), 1300 (SBA-15(C)-1300) and 2000 (SBA-15(C)-2000). The nonsteroidal anti-inflammatory drug (NSAID) diclofenac sodium was selected as a model drug and encapsulated into the pores of prepared supports. Materials were characterized by the combination of infrared spectroscopy (IR), atomic force microscopy (AFM), transmission electron microscopy (TEM), photon cross-correlation spectroscopy (PCCS), nitrogen adsorption/desorption analysis, thermogravimetry (TG), differential scanning calorimetry (DSC) and small-angle X-ray diffraction (SA-XRD) experiments. The drug release from prepared matrixes was realized in two model media differing in pH, namely small intestine environment/simulated body fluid (pH = 7.4) and simulated gastric fluid (pH = 2), and at different temperatures, namely normal body temperature (T = 37 °C) and inflammatory temperature (T = 42 °C). The process of drug loading into the pores of prepared materials from the diclofenac sodium salt solutions with different concentrations and subsequent quantitative determination of released drugs was analyzed by UV-VIS spectroscopy. Analysis of prepared SBA-15 materials modified with polyethylenimines in solution showed a high ability to store large amounts of the drug, up to 230 wt.%. Experimental results showed their high drug release into the solution at pH = 7.4 for both temperatures, which is related to the high solubility of diclofenac sodium in a slightly alkaline environment. At pH = 2, a difference in drug release rate was observed between both temperatures. Indeed, at a higher temperature, the release rates and the amount of released drug were 2–3 times higher than those observed at a lower temperature. Different kinetic models were used to fit the obtained drug release data to determine the drug release rate and its release mechanism. Moreover, the drug release properties of prepared compounds were compared to a commercially available medicament under the same experimental conditions.

Hydrophilic carboxyl supported immobilization of UiO-66 for novel bar sorptive extraction of non-steroidal anti-inflammatory drugs in food samples

Herein, the preparation of UiO-66 on frosted glass rod (FGR) was proposed through the coordination interaction of Zr-OH groups and carboxyl sites on FGR. The relative standard deviations (RSDs) of intra-batch and inter-batch were below 8.0% (n = 7). UiO-66-modified FGR (UiO-66@FGR) was applied to the extraction and monitoring of five non-steroidal anti-inflammatory drugs (NSAIDs) by coupling to novel bar sorptive extraction (BSE) with ultra-high performance liquid chromatography (UPLC). Sample volume, stirring rate, extraction time, sample pH value, desorption solvent, and desorption time were investigated. NSAIDs (ketoprofen, flurbiprofen, ibuprofen, naproxen, and diclofenac sodium) were determined at a low limit of detection (0.92 ng/mL) over a wide linear range (10–1500 ng/mL). The developed method was used to analyze NSAIDs in sheep muscle, chicken wing, and milk with recoveries of 80.8%-117.2%, RSDs < 6.5%. Fabricated UiO-66@FGR exhibited excellent reproducibility, stability, and good adsorption property towards NSAIDs in food samples.

Histopathological aspects of co-administration of dexamethasone and diclofenac sodium on male albino rats

Background and objective: Treatment of an animal with dexamethasone will result in sinuses extension, fat accumulation in the liver, and enlargement of hepatocytes. Whereas, non-steroidal anti-inflammatory drugs (diclofenac sodium) administration may lead to degeneration and formation of wide areas in the form of sinusoidal. Hydropic degeneration possibly is seen in the tubular epithelial cells of the kidney tissue. This study aimed to assess the toxic and side effects of dexamethasone and diclofenac sodium on the liver and kidney in rats, whether used separately or together. Methods: A total of 40 male albino rats were divided into four groups of ten in each, including the control group. One set was treated with dexamethasone (1.6 mg/kg/day), the other was treated with diclofenac sodium (30 mg /kg/day), and the last was treated with both drugs together at the same dose without mixture. Both drugs were administered intramuscularly for 30 days. Sections from the liver and kidney were stained by Hematoxeline and Eosin, then examined under a microscope. Results: Histopathological variation in the liver and kidney tissue of the treated animals have revealed that each drug (dexamethasone, diclofenac sodium) showed a significant alteration. Strong changes (+ + +) were observed in kidney tissue include degeneration, inflammatory aggregation, fibrosis, and edema, whereas in liver showed central vein dilatation, necrosis, and kupffer cells hyperplasia. Treating with the two drugs together, less alteration (+) in the tissues was noticed. Conclusion: The effect of both used drugs (dexamethasone and diclofenac sodium) was observed on the liver and kidney tissues of the experimental animals (rats) regardless of being applied separately or the two together. A probable inhibition role of the two drugs on each other have been noticed that lead to call for more detail investigation on this matter in years to come.

UV Spectroscopic Method for Optimization and Determination of Glibenclamide in Bulk, Pharmaceutical Dosage Form and its Application for In Vitro Interaction Studies

A simple, easy and cost-efficient UV spectroscopic method was developed and validated for glibenclamide, the second generation of sulfonylureas, using 0.1 N NaOH as a solvent. The proposed method is linear (R2 > 0.999) with the range 5–25 µg mL−1, accurate (99.60%), precise (inter and intraday variation 0.241 and 0.019%, respectively) and robust (< 1%). The quantification and detection limit were 1.46 and 0.48 μg mL−1, respectively. The validated method was applied for in vitro interaction studies of glibenclamide (GLB) with commonly prescribed quinolones (ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin) and nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium, ibuprofen, mefenamic acid, and aspirin) using UV spectrophotometer. The in vitro interaction studies were carried out in different artificially prepared physiological buffers at 37 °C for 2 h. Results showed raised level of glibenclamide when interacted with gemifloxacin (pH 7.4), levofloxacin (pH 9), ciprofloxacin (pH 4.5) and with moxifloxacin (pH 4.5, 7.4 and 9). Interaction with NSAIDs results in increased %availability of glibenclamide in the presence of diclofenac sodium, ibuprofen, and mefenamic acid at pH 4.5. The anticipated method can be successfully applied for the routine analysis and also for the interaction of glibenclamide with other drugs.

Ionisable substances chromatography: A new approach for the determination of Ketoprofen, Etoricoxib, and Diclofenac sodium in pharmaceuticals using ion – pair HPLC

An ion-pair HPLC method was developed and validated to analyze three of non-steroidal anti-inflammatory drugs (Ketoprofen, Etoricoxib, and Diclofenac sodium) in their pure and pharmaceuticals based on their ionisable characteristics. Cetyltrimethylammonium bromide (Cetrimide) was used as an ion pair reagent since it had not been used before for this purpose. Chromatographic analysis was accomplished using the C18 (250 × 4.6 mm, 5μm) column. Mobile phase consisted of a mixture of 50% Cetrimide10−3 M and 50% acetonitrile to analyze Ketoprofen and Etoricoxib, whereas for Diclofenac sodium, mobile phase was a mixture of 30% Cetrimide10−3 M and 70% acetonitrile. pH value was adjusted if necessary to 10 with ammonium hydroxide. The flow rate was 1mL/min and detection wavelengths were at 254 nm, 234 nm, and 254 nm for Ketoprofen, Etoricoxib, and Diclofenac sodium; respectively under ambient temperature. Retention times (Rt) were 9.41, 7.34, and 6.66 for Ketoprofen, Etoricoxib, and Diclofenac sodium; respectively. The proposed method was evaluated for linearity, accuracy, precision, and specificity according to ICH guidelines. Ketoprofen, Etoricoxib, and Diclofenac sodium were detected in the following linear ranges: (0.031–0.500mg/mL), (0.007–0.110g/mL), and (0.016–0.250mg/mL); respectively with excellent mean recovery values (98.0–102.0%). RSD% was in an acceptable range (less than 2), proving the precision of the developed method. Specificity was proved in the presence of degradation products. Furthermore, a comparison between the results of this study and the reported HPLC methods indicated that this developed method was better in terms of simplicity, analysis time, and no use of buffers in the mobile phase. In conclusion, the developed method can successfully detect Ketoprofen, Etoricoxib, and Diclofenac sodium quantitatively and qualitatively in their dosage forms without any interference with excipients, making this method valuable, reliable, and practical to be applied in quality control laboratories.

Phytol anti-inflammatory activity: Pre-clinical assessment and possible mechanism of action elucidation

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1β. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1β dependent pathways.

Adult post-tonsillectomy pain management: Opioid versus non-opioid drug comparisons

Objective: The primary purpose of this retrospective study was to determine if a non-steroidal anti-inflammatory drug (diclofenac sodium) plus acetaminophen was as effective as alternative opioid drug regimens, +/- ibuprofen and acetaminophen, for pain management in adults following tonsillectomy. Study design: Retrospective study. Setting: 4 hospitals in Michigan associated with the Detroit Medical Center. Subjects and methods: Medical records of adult tonsillectomy patients (age 18 to 50 Years) were reviewed. The incidences of unscheduled post-operative visits to either the ER or ENT clinic for uncontrolled throat pain and/or postoperative bleeding complications were reviewed.

Synthesis and biological activity evaluation of new thiazolidinone-diclofenac hybrid molecules

A novel series of [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid N`-3-(substituted)-4-thiazolidin-5-ylidenemethyl-hydrazide derivatives has been designed and synthesized. The structures of synthesized compounds were confirmed by their 1H NMR, 13C NMR and LCMS spectroscopic data. Target compounds were screened for their in vitro anticancer activity according to US NCI protocols, in vitro trypanocidal activity toward Trypanosoma brucei brucei (Tbb) and evaluated for anti-inflammatory activity on the carrageenan edema model in rats. Biological screening data led to identification of compounds 3.3 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N`-(4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-hydrazide) and 3.7 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N`-(4-oxo-2-thioxo-3-(3-trifluoromethylphenyl)thiazolidin-5-ylidenemethyl)-hydrazide) which demonstrated moderate antitumor activity on the non-small-cell lung cancer NCI-H522 and colon cancer HCT-116 cell lines. Several hit compounds (3.2, 3.4) exhibited the promising and significant inhibition growth of the parasites at micromolar concentrations (IC50 values of 4.8 and 7.06 μM, respectively). The synthesized compounds also demonstrated considerable anti-inflammatory effect comparable to the reference non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac sodium or ketorolac tromethamine.

Effect of α-adrenergic blockers silodosin in the management of distal ureteric calculus

Background: Urinary calculus disease is one of the 3 most common urological diseases. It affects about 12% of the world population and has become a worldwide health problem. Of all the urinary tract stones 20% are ureteral stones, of which 70% are found in the distal ureter. The objective of the study is to study the effect of silodosin in the passage of calculi in the distal ureter compared to non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium) and oral fluids.Methods: This study included a total of 90 patients between the study period from October 2016 to October 2018. 45 patients were chosen randomly and advised to take plenty of oral fluids and treated with NSAIDs and the other 45 patients were treated with silodosin 8 mg HS for one month along with oral fluids and NSAIDs. After 1 month if the stone was passed successfully, it was confirmed with ultrasonography, if failed, advised for surgery.Results: Majority of the patients were in the age group of 20-45 yrs. The mean size of the calculus was 5.60 cm on the right side and 5.71 cm on the left side. Out of the 45 patients who were on treatment with silodosin 35 patients had passed the calculi and 10 patients had no results with a success rate of 77.7%. In the 45 patients who were not on silodosin, 8 patients passed the calculi and 37 patients did not pass the calculi. 21 patients among the 45 underwent urethrorenoscopy.Conclusions: Silodosin is an effective and safe drug in the management of calculi in the distal ureter.

Evaluation of Phytochemical Content, Antibacterial Properties and Anti-inflammatory Activity of Andrographis echioidies (L) Nees

Background: There is much investigation with the Andrographis paniculata which is a very well-known medicinal plant, people were using this plant from ancient years, but this another species Andrographis echioides was not explored too much for many years. In this study we tried to find out the important phyto constitiuents, antibacterial activity and anti-inflammatory activity of this plant.&#x0D; Aim: The main aim of the present study, was to screen phytochemical derivatives from an Indian medicinal plant Andrographis echioides (L) Nees and to evaluate the antibacterial potential, and anti-inflammatory activity also.&#x0D; Study Design: Various tests or experiment was done in this study according to the review of the literature with little modification, a preliminary phytochemical screening was carried out in the plant extracts using qualitative methods. The whole plant of Anrographis echioides was subjected to soxhlet extraction using organic solvent of methanol, acetone, and petroleum ether. The antibacterial activity of acetone, methanol and petroleum ether whole plant extracts of Andrographis echioides was carried out using agar well diffusion method, anti-inflammatory activity was checked using fresh egg albumin method, and a statistical analysis was done using SPSS to prove that there is a strong correlation between the activity of our plant sample and a standard commercial drug (NASID).&#x0D; Place and Duration of the Study: The whole study was done in Panskura Banamali College, Vidyasagar University, Department of Biotechnology sponsored by BOOST, Louis Pasteur laboratory, West Bengal, India. The study was done between 17th August 2018 - 30th February 2019. &#x0D; Results: All these tests were done triplicate and the mean value was taken. The phytochemical analysis reveals that the plant has some important phytoconstituents such as Tannins, flavonoids, phenolic compounds, glycosides and terpenoids. The Acetone and Methanol extracts are showed the best zone of inhibition against the severe pathogens such as S. aureus (A.E-33 mm, M.E-28 mm), S. typhi (A.E- 26.67 mm, M.E-28.33 mm). The methanolic extract of Andrographis echioides showed excellent anti-inflammatory activity comparing to the NASID (Non-steroidal anti-inflammatory drugs) Diclofenac sodium, it showed almost same activity.&#x0D; Conclusion: Experimental findings reveal Andrographis echioides is the best herbal to control specially S. typhi, E. coli, S. aureus, K. pneumoniae. The phytochemical constituents which are responsible for many pharmacological activities, may be useful for the evolution of pharmaceutical and for the therapy of ailments, and also can used as a an potent anti-inflammatory natural remedy without any side effect.

Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches.

The purpose of this study was to apply the Quality by Design (QbD) approach to the electrospinning of fibres loaded with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin (INDO) and diclofenac sodium (DICLO). A Quality Target Product Profile (QTPP) was made, and risk assessments (preliminary hazard analysis) were conducted to identify the impact of material attributes and process parameters on the critical quality attributes (CQAs) of the fibres. A full factorial design of experiments (DoE) of 20 runs was built, which was used to carry out experiments. The following factors were assessed: Drugs, voltage, flow rate, and the distance between the processing needle and collector. Release studies exhibited INDO fibres had greater total release of active drug compared to DICLO fibres. Voltage and distance were found to be the most significant factors of the experiment. Multivariate statistical analytical software helped to build six feasible design spaces and two flexible, universal design spaces for both drugs, at distances of 5 cm and 12.5 cm, along with a flexible control strategy. The current findings and their analysis confirm that QbD is a viable and invaluable tool to enhance product and process understanding of electrospinning for the assurance of high-quality fibres.