Diclofenac Research Articles

A biomass composite based on natural deep eutectic solvent and magnetic chitosan for the solid phase extraction of PPCPs

Water pollution has always been a concern. The synergistic function of deep eutectic solvents (DESs) and adsorbent materials has aroused continuous attention, especially in terms of water pollution. In this study, four natural DESs were synthesized from choline chloride ([ChCl]) with glucose ([Glu]), fructose ([Fru]), sucrose ([Suc]) and maltose ([Mal]), respectively. The DESs were then coated onto the surface of magnetic chitosan (MCS) to form DESs-MCS composites. The structures of the DESs-MCS were confirmed by XRD, FT-IR, VSM, TGA and TEM. Afterwards, the DESs-MCS was combined with solid phase extraction (SPE) to separate PPCPs (production and extensive application of pharmaceuticals and personal care products) including diclofenac sodium salt (DCF) and tetracycline (TC). [ChCl][Fru]-MCS was selected as a representative adsorbent to extract DCF, and some influencing factors such as the mass of the [ChCl][Fru]-MCS, the volume of the DCF solution and the type of the desorption solvent were systematically investigated. Moreover, the adsorption of DCF was well conformed to the Langmuir adsorption isotherm and the Pseudo-Second-Order kinetic model. The maximum adsorption capacity of [ChCl][Fru]-MCS on DCF was up to 180.2 mg∙g−1. Furthermore, the relationship between solution pH and adsorption capacity, combined with XPS and FT-IR analysis of the [ChCl][Fru]-MCS before and after adsorption, were explored to get insight into the adsorption mechanism. It turned out that the electrostatic interactions play a vital role in the extraction process, and the hydrogen bonding was also considered as the main driving force based on the types of the functional groups of DES (such as –OH, –NH2). At last, the practical applicability of the [ChCl][Fru]-MCS was evaluated by performing the regeneration experiments and analyzing the real sample. The results demonstrated that the [ChCl][Fru]-MCS could be recycled six times without significant loss of adsorption capacity and the [ChCl][Fru]-MCS could be successfully applied to extract DCF from environmental water samples. The limit of detection and limit of quantification obtained for DCF were 0.27 and 0.90 μg∙mL−1, respectively. The RSDs of the precision and repeatability experiments were 0.71 % and 0.35 %, respectively. Hence, the prepared DES-MCS proved to be a potential adsorbent in the field of wastewater.

Preparation and performance of novel bio-nanocomposite ZnMg@PH for the removal of hazardous brilliant green, crystal violet, and diclofenac sodium

Preparation and performance of novel bio-nanocomposite ZnMg@PH for the removal of hazardous brilliant green, crystal violet, and diclofenac sodium

Cu quantum dots anchored core-shell submicrosphere catalyst for electro-enhanced degradation of diclofenac sodium

The low mass transfer efficiency, sluggish redox cycles of metal ions, and poor recycling rate of S2O82-→SO42-→S2O82- greatly limit the application of two-dimensional (2D) electrodes and persulfate (PS) techniques. In this study, an interface engineering strategy was developed to anchor Cu quantum dots (CuQDs) onto a novel Cu-CoO@NC (N-doped carbon) core-shell submicrosphere catalyst. The 3D electrochemical system (2D electrodes combined with Cu-CoO@NC particle electrodes) exhibited excellent catalytic behavior with 99.1 % removal of diclofenac sodium in 30 min. The Cu-CoO@NC catalyst presented effectiveness and strong environmental adaptability in a broad pH range, in actual water bodies, and for multiple PPCPs. Based on the results analyses of experiments and density functional theory (DFT) calculations, the excellent performances of Cu-CoO@NC/PS during electrochemical oxidation (EO) result from the effective mass transfer, efficient interfacial charge transport, rapid redox cycling of bimetallic ions promoted by cathode, repetitive cycle of S2O82- → SO42- → S2O82- caused by anode and multiple active sites of PS.

Development of an RP-HPLC Method for Quantifying Diclofenac Diethylamine, Methyl Salicylate, and Capsaicin in Pharmaceutical Formulation and Skin Samples.

An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical formulation and rabbit skin samples. The separation was achieved using a Thermo Scientific ACCLAIMTM 120 C18 column (Waltham, MA, USA, 4.6 mm × 150 mm, 5 µm). The optimized elution phase consisted of deionized water adjusted to pH = 3 using phosphoric acid mixed with acetonitrile in a 35:65% (v/v) ratio with isocratic elution. The flow rate was set at 0.7 mL/min, and the detection was performed at 205 nm and 25 °C. The method exhibits good linearity for capsaicin (0.05-70.0 µg/mL), methyl salicylate (0.05-100.0 µg/mL), and diclofenac diethylamine (0.05-100.0 µg/mL), with low LOD values (0.0249, 0.0271, and 0.0038 for capsaicin, methyl salicylate, and diclofenac diethylamine, respectively). The RSD% values were below 3.0%, indicating good precision. The overall greenness score of the method was 0.61, reflecting its environmentally friendly nature. The developed RP-HPLC method was successfully applied to analyze Omni Hot Gel® pharmaceutical formulation and rabbit skin permeation samples.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial.

Introduction Surgical removal of an impacted third molar is one of the most common oral surgical procedures performed in dental offices. The postoperative phase is often associated with severe inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually prescribed to manage postoperative discomfort. NSAIDs have been associated with gastrointestinal bleeding, renal function disturbances, and platelet count reductions. Thus, the present study demonstrates the utility of aescin in managing postoperative discomfort after the surgical removal of impacted mandibular third molars. This study aimed to correlate and compare the impact of aescin and diclofenac on salivary PGE2 levels and serum C-reactive protein levels after surgical extraction of the mandibular third molar. The study will also evaluate and compare the effectiveness of individual drug therapy in managing postoperative pain, swelling and mouth opening. Methods The planned study is a single-center, double-blind, randomized, parallel, prospective clinical trial. Each patient will be prescribed either diclofenac sodium 150 mg/day or aescin (escin) 120 mg/day to be taken orally in divided doses for five days after surgically removing the impacted mandibular third molar. Pain will be assessed using a visual analog scale. Facial swelling and mouth opening will be recorded using a metric scale with standardized reference points. ELISA (enzyme-linked immunosorbent assay (ELISA) will be employed to measure salivary Prostaglandin E2 and serum C–reactive protein levels. All parameters will be recorded preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2). Conclusion The proposed study is expected to show a clinically acceptable response to the administration of aescin for the management of postoperative discomfort compared to diclofenac sodium after third molar surgery. The proposed study is expected to positively manipulate the levels of salivary Prostaglandin E2 and serum C–reactive protein, which are reliable inflammatory markers. The outcome of this study may provide an efficacious and safe alternative to conventional nonsteroidal anti-inflammatory drugs for managing postoperative discomfort following third molar surgery.

Evaluation of polyherbal gel for musculoskeletal injuries in industrial workers.

Industrial workers often have musculoskeletal disorders due to the nature of their work. The goal was to investigate the scientific use of polyherbal gel in relieving pain and stiffness due to musculoskeletal injuries and improving activities of daily living (ADLs) in industrial workers. A pragmatic, single-blinded, randomized control study divided 200 musculoskeletal injury patients into four parallel groups (n = 50). Groups 1 and 2 were applied polyherbal gel via phonophoresis with therapeutic ultrasound and superficial massage. Groups 3 and 4 received diclofenac diethyl-ammonium 1% gel by phonophoresis and superficial massage. The Global Pain Relief Scale, Numeric Pain Rating Scale (NPRS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to measure pain, stiffness, and ADLs. Data was analyzed using one-way analysis of variance (ANOVA) and paired t-test to compare mean±SD of four independent groups before and after gel application. The confidence interval was 95%, with p < 0.05 considered significant. The results revealed that polyherbal gel reduced pain (NPRS, WOMAC and Global pain relief scales) more efficiently (p≤0.000) when applied with phonophoresis as compared to applied with massage and standard diclofenac (p≤0.005), furthermore, polyherbal gel when applied with phonophoresis showed more efficient results. Industrial workers with musculoskeletal injuries benefited from the use of polyherbal gel for pain and inflammation relief. The polyherbal gel is natural, cost-effective, and easy to formulate.

Unraveling the role of Mn(V)/Mn(III) in the enhanced permanganate oxidation under Vis-LED radiation

A novel approach of visible light-emitting diode (Vis-LED) radiation was employed to activate permanganate (Mn(VII)) for efficient organic micropollutant (OMP) removal. The degradation rates of OMPs by Vis-LED/Mn(VII) were 2–5.29 times higher than those by Mn(VII) except for benzoic acid and atrazine. Increasing wavelengths (445–525 nm) suppressed the degradation of diclofenac (DCF) and 4-chlorophenol (4-CP) owing to the decreased quantum yields of Mn(VII). Comparatively, light intensity and Mn(VII) dosage had a positive effect on the degradation of DCF and 4-CP. Experimental data revealed that Mn(V) dominated the DCF degradation whereas Mn(III) was the active oxidant in the 4-CP degradation. Mn(V) and Mn(III) formed from the photo-decomposition of Mn(VII), meanwhile, Mn(III) also formed from the Mn(V) photo-decomposition. The increase in solution pH inhibited DCF degradation but had a positive impact on 4-CP degradation, mainly due to the changing speciation of DCF and 4-CP. Inorganic anions (Cl− and HCO3−) had little impact on DCF and 4-CP degradation, while humic acid (HA) showed a positive impact because of the π-π interaction between HA and DCF/4-CP. The transformation products of DCF and 4-CP were identified and transformation pathways were proposed. Finally, the Vis-LED/Mn(VII) exhibited great degradation performance in various authentic waters. Overall, this study boosts the development of Mn(VII)-based oxidation processes.

Evaluation of Anticancer, Anthelminthic, Anti-Nociceptive, Antidiabetic and Toxicological Investigation of Ludwigia adscendens

The present research investigated Ludwigia adscendens crude methanol extract invitro anticancer anthelminthic, and invivo anti-nociceptive, antidiabetic and toxicological properties. The coarsely dried plant powder was extracted using methanol. The methanolic extract (MELA) was further tested for anticancer, anthelminthic, anti-nociceptive, antidiabetic and toxicological activities. Cell Viability Assay was used for anticancer testing, and the earthworm assay was used for anthelminthic testing using different concentrations. Antinociceptive tests were done on Swiss albino mice at 200 and 400 mg/kg utilizing a hot plate, acetic acid induced writhing &amp; formalin-induced paw licking tests. Antidiabetic test was done using Blood Glucose Determination test using the dose of 150 mg/kg and 300 mg/kg. Acute toxicity was tested utilizing cinnamon oil-induced toxicological tests at 3000, 5000 and 7000 mg/kg. The MELA demonstrated 39.16% inhibition at 1000µg/mL in the Cell Viability Assay. The earthworm died after 6 minutes and 4 seconds in the 100 mg/mL anthelminthic test, whereas Albendazole killed it in 4 minutes and 20 seconds. Hot plate test results were substantial. The formalin-induced nociception test demonstrated strong inhibition rates of 79.54% in the early phase and 74.54% in the late phase at 400 mg/kg, compared to 62.99% and 68.18% for diclofenac sodium. Acetic acid-induced writhing test showed 77.66% of pain inhibition where’s Diclofenac sodium showed 79.61%. MELA inhibited blood glucose level very significantly compared to the standard Glibenclamide. In toxicological testing, 7000 mg/kg killed mice 2/5, whereas cinnamon oil killed 5/5 within 24 hours. The study shows that MELA has moderate anticancer, significant anthelmintic, anti-nociceptive, antidiabetic and mild toxicological properties. They may support the plant's use in conventional medicine to relieve pain, minimize drug intoxication, and prevent cancer, control diabetes and parasitic disorders.

Exploring diclofenac potassium adsorption on activated carbon: A comprehensive statistical physics and experimental approach

This study aims to contribute to understanding the removal processes of diclofenac potassium (DP) medicine in wastewater treatment systems, employing activated carbon (AC) as an adsorbent. To achieve this goal, a multidisciplinary approach was adopted, integrating experimental and theoretical analyses of equilibrium data regarding the adsorption of DP on AC. Five statistical physics models were applied to determine the model best for the adsorption process. The selection of the most appropriate model considered both the performance of the models and the analysis of the estimated parameters. Statistically, all models exhibited satisfactory results. However, when analyzing the estimated parameters, the double-layer model with single adsorption energy emerged as the most suitable model to describe the analyzed process. Based on the chosen model’s parameters, we observed that as the temperature increases, the number of active sites occupied during adsorption and their availability on the adsorbent also increases. However, the number of available adsorption sites decreases as the temperature rises. The half-saturation concentration, in turn, increases with increasing temperature, suggesting that the process is favored when temperatures above room temperature are used. Additionally, higher temperatures provide better removal results, indicating that DP molecules’ non-parallel and parallel orientations on the AC surface favor the adsorption process. Finally, our combined results led to the proposal of a mechanism for DP adsorption on AC, which is based on physical adsorption interactions between adsorbate-adsorbent and adsorbate–adsorbate.

Process optimization for the removal of sodium diclofenac from water using a green polymeric membrane

New polymeric membranes for water treatment have been regularly developed and reported by the scientific community; however, process optimization based on the application purpose is necessary to achieve the best performance. In this work, a previously developed “green” polymeric membrane was employed to investigate the influence of process parameters on the removal of sodium diclofenac (DCF) from water. The “green” classification relies on the membrane components (poly(vinyl alcohol) – PVA, citric acid, glycerol, and green synthesized silver nanoparticles) and the mild conditions for its preparation. The parameters studied were the compaction and operational pressure (1.0 – 5.0 bar), feed temperature (10 – 25 °C), DCF concentration (0.002 – 0.010 g L−1), and feed pH (4.0 – 10.0). The results showed a positive influence of pressure on DCF removal (from 54 % to 75 %, within a range of 1.0–5.0 bar) due to the PVA structure densification, as well as the temperature (from 61 % to 82 %, within a range of 10–25 °C) because of the increased water affinity. The DCF concentration influenced the absorption of DCF into the membrane, reaching the maximum of 73 % of DCF removal at 0.007 – 0.010 g L−1. The feed pH determined the mechanism of removal but had a minor influence on the final performance (from 73 % of DCF removal at acidic pH to 77 % at alkaline conditions). The optimized conditions of 5 bar, 25 °C, 0.008 g L−1 DCF, and pH ∼5.75 promoted a permeability of 0.024 L m−2 h−1 bar−1 with 80 % DCF removal. This performance is comparable to that observed for commercial nanofiltration membranes but offers the advantage of a membrane fabricated and operated using a sustainable approach.

Self-Assembled Multilayer-Modified Needles Simulate Acupuncture and Diclofenac Sodium Delivery for Rheumatoid Arthritis.

A novel therapeutic approach combining acupuncture and diclofenac sodium (DS) administration was established for the potential treatment for rheumatoid arthritis (RA). DS is a commonly used anti-inflammatory and analgesic drug but has short duration and adverse effects. Acupoints are critical linkages in the meridian system and are potential candidates for drug delivery. Herein, we fabricated a DS-loaded multilayer-modified acupuncture needle (DS-MMAN) and investigated its capacity for inhibiting RA. This DS-MMAN possesses sustained release properties and in vitro anti-inflammatory effects. Experimental results showed that the DS-MMAN with microdoses can enhance analgesia and efficiently relieve joint swelling compared to the oral or intra-articular administration of DS with gram-level doses. Moreover, the combination of acupoint and DS exerts a synergistic improvement in inflammation and joint damage. Cytokine and T cell analyses in the serum indicated that the application of DS-MMAN suppressed the levels of pro-inflammatory factors and increased the levels of anti-inflammatory factors. Furthermore, the acupoint administration via DS-MMAN could decrease the accumulation of DS in the liver and kidneys, which may express better therapeutic efficiency and low toxicity. The present study demonstrated that the acupuncture needle has the potential to build a bridge between acupuncture and medication, which would be a promising alternative to the combination of traditional and modern medicine.

Distinguishing the transitions of fluorescence spectra of tryptophan-134 and 213 in BSA induced by bindings of UV filters, oxybenzone-3, and avobenzone

Abstract Oxybenzone-3 (OBZ) and avobenzone (ABZ), commercially available ultraviolet-light filters for sunscreens, are known to induce photosensitizing allergy as an adverse effect, similar to an analgesic ketoprofen (KTP) due to their benzophenone moiety. The present study focused on OBZ and ABZ's protein binding compared to the related analgesics, KTP, diclofenac (DCF), and ibuprofen (IBP). The bovine serum albumin (BSA) was used as a protein model, measuring the fluorescent spectral peak shifts (i) and Stern–Volmer analysis (i) of its intrinsic tryptophans. Moreover, their adsorption types (iii) were verified using the singular value decomposition (SVD) computation of fluorescence spectra. For (i), (ii), and (iii), KTP and DCF caused a no-shift peak, an ordinary dynamic quenching, and a simple Langmuir adsorption. We found OBZ exhibiting (i) red-shift and (ii) including static quenching, ABZ suggesting (i) blue-shift and (iii) binding to multiple bind sites, and IBP indicating (i) blue-shift and (iii) multivalent bindings. Integrating the results, it can be understood that OBZ interacts with subdomain IA (around W134) in BSA, while ABZ interacts with subdomain IIA (around W213) in BSA. Moreover, IBP is bound to BSA with a cooperative effect, certified by Hill's plot. OBZ and ABZ had their individual binding sites on a protein, suggesting the exchange between OBZ and ABZ might reduce their own adverse effect. The present study verified the effectiveness of the SVD computation in distinguishing the details of the adsorption manner of ligands around the intrinsic fluorescent probes.

Comparative Anti-inflammatory Activity of a Nanocomposite-Based Herbal Oral Rinse and a Commercial Oral Rinse.

The present study aimed to evaluate and compare the anti-inflammatory effects of two oral rinse formulations, a commercial oral rinse and anOcimum tenuiflorum and Ocimum gratissimum(nanocomposites, NCs) oral rinse, using in vitro assays commonly employed to assess anti-inflammatory activity. The anti-inflammatory potential of the oral rinse formulations was assessed using bovine serum albumin (BSA) denaturation, egg albumin denaturation, and membrane stabilization assays. Diclofenac sodium was used as a reference standard in all assays. The inhibition percentages of BSA denaturationand egg albumin denaturation assays, as well as membrane stabilization effects, were measured at various concentrations of the oral rinse formulations. Both the commercial oral rinse and theOcimum tenuiflorum and Ocimum gratissimumoral rinse demonstrated significant inhibition of BSA denaturation, indicating their anti-inflammatory potential. TheOcimum tenuiflorum and Ocimum gratissimum (NCs) oral rinse consistently showed higher inhibition percentages than the commercial oral rinse, suggesting stronger anti-inflammatory effects in this assay. In the egg albumin denaturation assay, both formulations exhibited inhibition of protein denaturation, with theOcimum tenuiflorum and Ocimum gratissimum(NCs) oral rinse showing comparable or slightly higher inhibition percentages. The membrane stabilization assay further supported the anti-inflammatory properties of both formulations, with theOcimum tenuiflorum and Ocimum gratissimum (NCs) oral rinse demonstrating efficacy comparable to diclofenac sodium. The results suggest thatOcimum tenuiflorum and Ocimum gratissimum (NCs) oral rinse may possess stronger anti-inflammatory effects compared tocommercial oral rinse, as evidenced by higher inhibition percentages in the BSA denaturation assay. Both formulations showed promising anti-inflammatory activity in the egg albumin denaturation and membrane stabilization assays, indicating their potential for mitigating inflammation. TheOcimum tenuiflorum and Ocimum gratissimum (NCs) oral rinse exhibits significant anti-inflammatory effects in vitro, potentially surpassing the efficacy of the commercial oral rinse. Further studies are needed to explore the clinical implications of these findings and to validate the anti-inflammatory properties of theOcimum tenuiflorum and Ocimum gratissimum (NCs) oral rinse in vivo.

High-efficiency removal of diclofenac sodium (DS) drug using chitosan-grafted-poly(acrylic acid-co-N-isopropylacrylamide)/kaolin clay hydrogel composite

ABSTRACT The current study mainly deals with the adsorptive removal of the diclofenac sodium (DS) drug from aqueous solution by the use of the kaolin-CS-g-poly(AA-co-NIPAM) composite. The synthesised composite was characterised by Fourier Transform infrared (FTIR), X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), Transmission electron microscopy (TEM), energy dispersive X-Ray spectroscopy (EDS), atomic force microscopy (AFM), swelling % ratio and point of zero charge ( p H PZC ). The pHpzc of the composite was determined to be 4. The maximum adsorption capacity of 18.51 mg/g observed at the optimised conditions, including 0.1 g of kaolin clay dose, at neutral pH using composite dose of 0.06 g for 90 min. The optimum drug concentration was 500 mg/l for temperature of 30°C. Effect of the ionic strength on the adsorption capacity of the composite and its mechanism for DS drug removal has also been investigated. The process of drug adsorption on the prepared composite was chemical and data fits well to the pseudo second order and Langmuir model. Overall, the process was spontaneous and endothermic in nature.

Analgesic Activity Combination of Dry Extract of Meniran Leaves (Phyllanthus niruri L.) and Moringa Leaves (Moringa oleifera L.) Using the Chemical Induction Method: Invivo Study

Analgesics are drugs that selectively reduce pain in the central nervous system or peripheral pain mechanisms without significantly changing consciousness. This study aims to determine the analgesic activity of a combination of dry extracts of meniran leaves (Phyllanthus niruri l.) and moringa leaves (Moringa oleifera l.) against Swiss Webster rats with chemical induction methods. This research proves the presence of secondary metabolite content in the dry extract of meniran leaves and moringa leaves which have analgesic activity. The research used 30 male Swiss Webster rats divided into 5 groups. Group 1 is the negative control (CMC-Na 0.5%), group 2 is the positive control (diclofenac Na), group 3 (Dry extract of meniran leaves), group 4 (Dry extract of moringa leaves) and Group 5 (Combination of dry extracts). meniran and moringa leaves). Each was given 1 mL of 1% acetic acid induction chemical stimulation, then the writhing response was observed and recorded at 5-minute intervals for 30 minutes. The results showed that the K3 group combined dry extract of meniran leaves (Phyllanthus niruri L.) and moringa leaves (Moringa oleifera L) is not statistically significantly different from the positive control diclofenac sodium, p-value = 0.183. In conclusion, dry extract of meniran leaves (Phyllanthus niruri L.) and Moringa leaves (Moringa oleifera L.) has been proven to contain secondary metabolites of flavonoids, alkaloids, tannins, and saponins which have analgesic activity.

Impact of Time on Parameters for Assessing the Microstructure Equivalence of Topical Products: Diclofenac 1% Emulsion as a Case Study.

The demonstration of bioequivalence proposed in the European Medicines Agency's (EMA's) draft guideline for topical products with the same qualitative and quantitative composition requires the confirmation of the internal structure equivalence. The impact of the shelf-life on the parameters proposed for internal structure comparison has not been studied. The objectives of this work were: (1) to quantify the effect of the time since manufacturing on the mean value and variability of the parameters proposed by the EMA to characterize the internal structure and performance of topical formulations of a complex topical formulation, and (2) to evaluate the impact of these changes on the assessment of the microstructure equivalence. A total of 5 batches of a topical emulgel containing 1% diclofenac diethylamine were evaluated 5, 14, and 23 months after manufacture. The zero-shear viscosity (η0), viscosity at 100 s-1 (η100), yield stress (σ0), elastic (G') and viscous (G″) moduli, internal phase droplet size and in vitro release of the active ingredient were characterized. While no change in variability over time was detected, the mean value of all the parameters changed, especially the droplet size and in vitro release. Thus, combining data from batches of different manufacturing dates may compromise the determination of bioequivalence. The results confirm that to assess the microstructural similarity of complex formulations (such as emulgel), the 90% confidence interval limit for the mean difference in rheological and in vitro release parameters should be 20% and 25%, respectively.

The safety and efficacy of diclofenac sodium suppository as adjunctive opioids in the treatment of cancer pain: A prospective, multi-center, real-world study.

12055 Background: Cancer pain is one of the most common and unbearable symptoms for cancer patients (pts), seriously affecting their quality of life. Diclofenac sodium is a potent third-generation non-steroidal anti-inflammatory drug known for its significant analgesic, anti-inflammatory, and antipyretic effects. It is commonly used to treat different types of cancer pain. The objective of this study was to assess the safety and effectiveness of diclofenac sodium suppository when used alongside opioids for managing cancer pain in pts with solid tumors. Methods: In this prospective, multi-center, real-world study, we enrolled pts diagnosed with malignancy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, numeric rating scale (NRS) score ≥ 3, and sustained cancer pain, who required additional analgesic medication were enrolled. Diclofenac sodium suppository is an anal administration suppository, prescribed once a day at a dosage of 50 mg. This study was conducted across 20 centers to observe the clinical characteristics of pain relief in pts with cancer pain . The primary endpoint of the study was to assess the safety of the medication. The secondary endpoints included evaluating the incidence of breakthrough pain (BP), NRS score, and Brief Pain Inventory (BPI) score on the second and sixth days of medication. Results: Of the 506 pts that were screened, 437 pts met the inclusion criteria. This included 10 pts who did not receive planned treatment and 2 pts who did not undergo post-baseline efficacy evaluation. Among the 425 pts in the full analysis set (FAS), 261 were man, and 169 (39.8%) had baseline BP. The mean age was 63.0±11.3 years old. Among 425 response-evaluable pts, compared to the baseline, the incidence of BP was reduced on the second (20.0% vs 39.8%), and sixth days (14.8% vs 39.8%) of medication and the difference was statistically significant ( P &lt; 0.001, P &lt; 0.001). For pts with baseline BP, 56.2% and 66.9% pts achieved BP relief on the second and sixth days of medication, respectively. From the baseline evaluation, the mean NRS scores for the three visits (baseline, second day, sixth day) were 5.28 ± 1.71, 3.73 ± 1.71, and 2.91 ± 1.88, respectively. The mean pain intensity at each visit was decreased compared to the baseline, and the difference was statistically significant ( P &lt; 0.001, P &lt; 0.001). 427 pts were included for safety analysis and 5 pts experienced any grade treatment emergent adverse events (TEAEs). All TEAEs were grade 1-2. TEAE leading to treatment discontinuation was occurred in one pt. Conclusions: This study demonstrated that diclofenac sodium suppository was an effective treatment option for managing breakthrough pain in patients with persistent cancer pain who required additional analgesic therapy. Moreover, diclofenac sodium suppository was found to be well tolerated when administered anally.

Forecasting the effect of water gastric emptying patterns on model drug release in an in vitro glass-bead flow-through system.

Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.

Phytochemical and pharmacological profiling of extracts of Pterygota alata (Roxb.) R. Br. leaves deciphered therapeutic potentialities against pain, hyperglycemia and diarrhea via in vivo approaches

Background and aimPterygota alata (Roxb.) R. Br. is a large, broad-leaved evergreen plant in the family Malvaceae (formerly Sterculiaceae). The present study aimed to investigate the phytochemical and pharmacological properties of methanolic extract of the leaves (200 mg/kg bw and 400 mg/kg bw) of P. alata focusing on analgesic, hypoglycemic, and anti-diarrheal potentials on the Swiss Albino mice model. MethodsGas chromatography and mass spectrometry (GC-MS) technique was employed to identify the bioactive compounds from the plant species. The tail flicking procedure and acetic acid-induced writhing inhibition were carried out to estimate central and peripheral analgesic properties. The anti-diarrheal property of the herbaceous extractive was assessed employing the castor oil-induced antidiarrheal approach, while the hypoglycemia was estimated employing the tail-tipping method. ResultsThe study reported a total of thirty-seven phytoconstituents by using GC-MS analysis, where erucamide (25.5 %), 8,11,14-Docosatrienoic acid, methyl ester (14.58 %), methyl linoleate (12.67 %), and methyl palmitate (9.23 %) were most abundant in the plant species. In evaluating central analgesia, the leaf extract of P. alata exerted significant central analgesic (200 mg/kg bw and 400 mg/kg bw) efficacy. The acetic acid-induced writhing was inhibited by 45.84 % and 66.67 % at both doses, demonstrating a promising peripheral analgesic effect compared to diclofenac sodium (75.00 %). On the contrary, hypoglycemic actions remained dosage and time-dependent. In the antidiarrheal activity assay, the number of diarrheal feces was reduced significantly by 40.00 % (200 mg/kg) and 68.00 % (400 mg/kg), correspondingly, which was comparable to the positive control loperamide (72.00 %). In addition, the study of acute oral toxicity revealed that the extracts of the plant species were found to be safe, with a median lethal dose (LD50) value greater than 1000 mg/kg. ConclusionThe current study supports the assertion that the P. alata plant species is rich in numerous phytoconstituents and has the potential for traditional application in managing pain, hyperglycemia, and diarrhea. Nonetheless, additional investigation is necessary to extract and identify the bioactive compounds from the plant, which is crucial for advancing the discovery of novel medicinal compounds aimed at addressing a range of health conditions.