Adjuvant Rectal Diclofenac for Post Operative Analgesia after Caesarean Section—A Randomized Controlled Study

BACKGROUND: Pain management following caesarean section still remains a challenge in our environment. Most potent analgesics are either not readily available or expensive. Diclofenac suppository is an NSAID that can be used for postoperative analgesia. It is available and affordable. OBJECTIVE: To compare the efficacy and safety of combined rectal diclofenac and intramuscular pentazocine with intramuscular pentazocine alone for post operative pain control following lower segment caesarean section. METHODOLOGY: A total of 120 women who met the selection criteria scheduled for caesarean section under spinal anaesthesia with bupivacaine were randomized into two equal groups to receive either 75 mg diclofenac suppository 12 hourly for 24 hours or one anusol suppository (the placebo) 12 hourly for 24 hours. Both groups received pentazocine as primary analgesia. RESULT: The primary outcome measure is the proportion of patients with severe pain at 24 hours using the visual analogue rating scale. Secondary outcome measures are the time from surgery to ambulation, Passage of flatus, maternal satisfaction and presence of complications. Statistical analysis was done using spss version 22 and graph pad statistical package. Student T-test was used for continuous variables whereas chi square was used for categorical variables P CONCLUSION: Adjuvant rectal diclofenac is superior to pentazocine alone in the management of pain after caesarean section. Less number of patients had moderate to severe pain at 24 hours post operation. Maternal satisfaction in relation to pain management is better with diclofenac suppository. The levels of complications were comparable in both groups.

Combinatorial effect of diclofenac with piperine and D-limonene on inducing apoptosis and cell cycle arrest of breast cancer cells

Objective:To investigate the potential synergistic activity of diclofenac with piperine and D-limonene in inducing apoptosis and cell cycle arrest in breast cancer MCF-7 cells.Methods:Molecular docking study was conducted to evaluate the binding affinity of diclofenac with piperine and D-limonene against p53,Bax,and Bcl-2.The MTT assay was used to determine IC50,and the Chou-Talay method was used to determine the synergistic concentration of the combination treatment of diclofenac plus piperine and diclofenac plus D-limonene.Apoptosis detection,cell cycle arrest,reactive oxygen species production,and mitochondrial membrane potential were also investigated.Results:Diclofenac,piperine,and D-limonene showed potent binding affinity for p53,Bax,and Bcl-2.Diclofenac plus piperine and diclofenac plus D-limonene enhanced the formation of reactive oxygen species,which also had an effect on the mitochondrial membrane’s integrity and caused DNA fragmentation.Diclofenac plus piperine and diclofenac plus D-limonene arrested the cells in the sub-G0phase while drastically lowering the percentage of cells in the G2/M phase.Furthermore,the elevated apoptosis in the combined therapy was confirmed by annexin V/propidium iodide staining.Conclusions:The combined therapy prominently enhanced the antiproliferative and apoptotic effects on MCF-7 cells compared with treatment with diclofenac,piperine,and D-limonene alone.

Holistic Approach in the Treatment of Actinic Keratosis: Benefits and Disadvantages of 5-Fluorouracil, Imiquimod, Diclofenac and Curaderm

Background Actinic keratosis is the most prevalent premalignant skin disorder in the white population. Current guidelines provide no clear recommendations about preferred treatments. Methods The parameters;effectiveness, treatment duration, recurrence, side effects and cost of treatment were investigated for three frequently used topical therapies which were then compared with a most recent developed topical therapy. Published clinical data obtained from the literature was used to compare these parameters for 5-fluorouracil, imiquimod and diclofenac and relate them with the newly developed Curaderm. Results A wide variation in the concentrations of the active anti-keratotic ingredients, application frequency, duration of treatment, recurrence rates and cost of treatment exist between the different topical therapies. The efficacy rates and side effects were less variable. Overall, Curaderm is the most suitable treatment for actinic keratosis. Clinical evidence is presented illustrating the effects of Curaderm on field-directed treatments and solitary treatments of actinic keratoses. Conclusions Current medical guidelines do not provide clear recommendations on which treatment approach for actinic keratosis is preferred. Direct head-to-head comparison between treatments with emphasis on efficacy, safety, treatment duration, compliance, convenience, cosmetic outcome, patient acceptance and cost should be available to the patient, the practising physician, healthcare system and should assist in therapeutic treatment guidelines and policymaking. Given the very favourable profiles of these parameters with Curaderm when compared with other home-based treatments, it should be considered that Curaderm is first-in-line.

Combination of Diclofenac Potassium and Propolis in the Therapy of Oral Aphthosis: A Randomized, Clinical, Double-Blind, Placebo-Controlled Study

Background: Oral aphthosis has a negative impact on oral health. This study aimed to assess the effectiveness of gel formulation including diclofenac and propolis in the treatment of oral ulcers. Methods: Participants included 100 normal individuals with aphthous, excluding those having allergies to any ingredient in the diclofenac formulation. Patients were randomly assigned into two groups: one group received treatment with a combination of diclofenac potassium 3% (10 mg/g, 60 g) and propolis 5% gel (Group II), and the other group received a placebo (Group 1). The patient was evaluated using standard digital photographs and chronic oral mucosal questionnaires on days 1, 3, 5, and 7 after healing. Utilizing the Mann-Whitney U test, the two groups were compared. Each group’s changes were examined using Friedman’s test. Results: There was a statistically dramatic change over time in Group II. After one day, the median total score dropped statistically significantly, and from one to three days with effect size (d) 2.485, Group II demonstrated 48% complete healing and 52% partial healing, while Group I demonstrated 4% partial healing and 96% no change. Effect size (V): 0.995. Conclusions: The combination of diclofenac and propolis provided instant relief and an affordable new regimen for treating oral aphthosis.

Randomized, Double-Blind, Double-Masked, Parallel Group Clinical Study to Compare the Effectiveness of Diclofenac Potassium 150 mg, LP OD, vs Diclofenac Potassium 50 mg, TID, Three Times a Day, in Knee Osteoarthritis

Background: Osteoarthritis is a chronic disease associated with pain, inflammation, stiffness and synovial effusion, with progressive functional limitation, compromising quality of life. It progressively leads to loss or decrease in joint function. Pharmacological and non-pharmacological therapy seeks symptomatic management, complicated by a lack of adherence. After acetaminophen, non-steroidal anti-inflammatory drugs such as diclofenac are the most widely used medications. Objectives: The primary objective compared the analgesic effect of diclofenac 150 mg once daily vs. 50 mg three times daily in patients with knee osteoarthritis. The secondary objective assessed changes in quality of life. Method: One group received diclofenac 150 mg OD with placebo TTD. Another group received placebo OD and 50 mg active diclofenac (reference) TTD, both for 30 days. The evaluation of pain was carried out by a visual analog scale (VAS), at the beginning, 2, 3, 4, 15 and 30 days, quality of life (the WOMAC scale) and adverse effects, at 15 and 30 days. Results: Pain decreased significantly on days 15 and 30, compared to day 0, in both groups, without differences between groups. The total results in the WOMAC scale showed a very marked improvement at 15 and 30 days, without differences between groups. The most frequent adverse effects were constipation 6% in the reference group, and gastric discomfort 30.3% in the reference group vs 28.1%, in the Test group. Conclusions: Prolonged-release diclofenac 150 mg OD is as effective as diclofenac 50 mg TID for the treatment of patients with knee osteoarthritis.

Bioequivalence Study of Diclofenac 150 mg XR: A Single-Dose, Randomized, Open Label, 2-Period Crossover Study in Healthy Adult Volunteers

Objectives: Evaluate the bioequivalence (BE) of two oral tablets formulations of diclofenac 150 mg in healthy male subjects under fasting condition. This was a phase I, randomized, open label, balanced, two period, two sequences, single oral dose, crossover, analyst blind study. Methods: Twenty four (24) healthy subjects were randomly assigned to one of two sequences protocol: 150 mg XR of reference formulation (R), diclofenac sodium in the first period or the test formulation (T), diclofenac potassium in the second or vice versa. The plasma concentrations were determined using a validated LC-MS/MS method. Pharmacokinetic (PK) parameters included: maximum plasma concentration (Cmax), area under the plasma concentration—time curve from time 0 to the last measurable concentration (AUC0-t), and area under the plasma concentration—time from time 0 to infinity (AUC0-∞), were evaluated for BE. Results: The results showed that 90% confidence intervals for the test/reference geometric mean ratios (GMR) of Cmax (90.43 - 107.17), AUC0-t (93.08 - 116.46) and AUC0-∞ (92.52 - 117.39) were within the BE (80% - 125%) acceptance range. Conclusions: Two formulations, reference product (R) Voltaren® (diclofenac sodium) of Novartis and test product (T), Diklason Bi (diclofenac potassium) of Laboratorios Leti S.A.V., with a single dose of 150 mg XR, under fasting conditions were bioequivalent. No severe, serious or unexpected adverse events (AEs) were reported in this study.

Exchange Reaction Characteristics of Anion Exchange Resin for Diclofenac Sodium

Aim To study the exchange reaction characteristics of anion exchange resin for diclofenac sodium. Methods The drug-resin complexes were prepared by a batch method with diclofenac sodium as the model drug and the strong anion exchange resin (201 × 7) as the carrier. The effects of different forms (OH~ - and Cl~ - ) of the strong anion exchange resin, the particle size of the resin, and the reaction temperature on the exchange behavior were described. The exchange kinetic profiles were fitted. The related exc...

Pharmacokinetics and Relative Bioavailability ofsustained-release Tablets of Diclofenac Sodiumin Male Volunteers

The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.

Efficacy of intramuscular diclofenac and fluid replacement in prevention of post-ERCP pancreatitis

AIM： TO assess the efficacy of intramuscular diclofenac and fluid replacement for prevention of post-endoscopic retrograde cholangiopancreatography （ERCP） pancreatitis.METHODS： A prospective, placebo-controlled study was conducted in 80 patients who underwent ERCP. Patients were randomized to receive parenteral diclofenac at a loading dose of 75 mg followed by the infusion of 5-10 mL/kg per hour isotonic saline over 4 h after the procedure, or the infusion of 500 mL isotonic saline as placebo. Patients were evaluated clinically, and serum amylase levels were measured 4, 8 and 24 h after the procedure.RESULTS： The two groups were matched for age, sex, underlying disease, ERCP findings, and type of treatment. The overall incidence of pancreatitis was 7.5% in the diclofenac group and 17.5% in the placebo group （12.5% in total）. There were no significant differences in the incidence of pancreatitis and other variables between the two groups. In the subgroup analysis, the frequency of pancreatitis in the patients without sphincter of Oddi dysfunction （SOD） was significantly lower in the diclofenac group than in the control group （ρ = 0.047）.CONCLUSION： Intramuscular diclofenac and fluid replacement lowered the rate of pancreatitis in patients without SOD.

Enhanced photocatalytic Cr(Ⅵ) reduction and diclofenac sodium degradation under simulated sunlight irradiation over MIL-100(Fe)/g-C_3N_4 heterojunctions

Metal‐organic framework MIL‐100(Fe)and g‐C3N4 heterojunctions(MG‐x,x=5%,10%,20%,and 30%,x is the mass fraction of MIL‐100(Fe)in the hybrids)were facilely fabricated through ball‐milling and annealing,and characterized by powder X‐ray diffraction,Fourier transform infrared spectroscopy,thermogravimetric analysis,transmission electron microscopy,UV‐visible diffuse‐reflectance spectrometry,and photoluminescence emission spectrometry.The photocatalytic activities of the series of MG‐x heterojunctions toward Cr(VI)reduction and diclofenac sodium degradation were tested upon irradiation with simulated sunlight.The influence of different organic compounds(ethanol,citric acid,oxalic acid,and diclofenac sodium)as hole scavengers and the pH values(2,3,4,6,and 8)on the photocatalytic activities of the series of MG‐x heterojunctions was investigated.MG‐20%showed superior photocatalytic Cr(VI)reduction and diclofenac sodium degradation performance than did the individual MIL‐100(Fe)and g‐C3N4 because of the improved separation of photoinduced electron‐hole charges,which was clarified via photoluminescence emission and electrochemical data.Moreover,the MG‐x exhibited good reusability and stability after several runs.

Hepatoprotective effect of Woodfordia fruticosa Kurz flowers on diclofenac sodium induced liver toxicity in rats

Objective:To evaluate the protective effect of Woodfordia fruticosa Kurz flowers against experimentally induced liver toxicity in rats.Methods:Two different doses of methanol extract of Woodfordia fruticosa(WFM) were evaluated for the hepatoprotective activity against diclofenac sodium induced hepatotoxicity in rats.Various biochemical parameters like alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total protein(TP),albumin(ALB),blood urea nitrogen(BUN) from serum;total protein(TP),glutathione (GSH) levels,catalase(CAT) and glutathione peroxidase(GPx) activities from liver were studied; histopathologic changes of liver were also evaluated.Results:WFM effectively reduced the elevated levels of serum ALT,AST,ALP and BUN,enhanced the reduced TP,ALB and hepatic GSH,CAT,GPx activity.The histopathological analysis suggested that WFM decreased the degree of liver fibrosis induced by diclofenac.Conclusions:This study demonstrates the hepatoprotective activity of WFM and thus scientifically support the use of this plant in traditional medicine for the treatment of liver disorders.

Comparative study of the efficacy and safety of bromfenac, nepafenac and diclofenac sodium for the prevention of cystoid macular edema after phacoemulsification

AIM： To compare the efficacy, tolerability and safety of bromfenac 0.09%, nepafenac 0.1% or diclofenac 0.1% for the prophylaxis of the cystoid macular edema（CME） after phacoemulsification. METHODS： Group sequential observational comparative study. After phacoemulsification, patients received two months for topical treatment of either diclofenac sodium, bromfenac or nepafenac. All patients received concomitant topical tobramycin 0.3% and topical prednisolone 1%. We measured CME using optical coherence tomography（OCT） central foveal thickness, macular thickness and total macular volume. RESULTS： We enrolled 243 patients from January to June 2015, and 35% received diclofenac, 32.9% bromfenac and 32.1% nepafenac. When we compared pre-operative to three weeks to two months, bromfenac was more effective in reducing foveal volume（21.3 and 35.4 mm3, respectively）, compared with the diclofenac（1.3 and 11.5 mm3, respectively）, and the nepafenac group, became more edematous 6.4 and 5.3, respectively. Totally 133 patients completed the post-surgical satisfaction questionnaire. Patients complained of eye stickiness in 13.8% whom we gave nepafenac, versus 10.3% whom we gave diclofenac sodium, and in 0 whom we gave bromfenac. CONCLUSION： Bromfenac is the best tolerated and is more effective than diclofenac and nepafenac in reducing CME after phacoemulsification.

Design and evaluation of a novel transdermal patch containing diclofenac and teriflunomide for rheumatoid arthritis therapy

The aim of this study was to design a compound transdermal patch containing diclofenac(DA)and teriflunomide(TEF)for the treatment of rheumatoid arthritis(RA).The various organic amines salts of DA were prepared and their forming was confirmed using DSC and FTIR.The percutaneous permeation of organic amines salt of DA was investigated in vitro using a two-chamber diffusion cell with excised rabbit skin as transdermal barrier.The formulation of the patch was optimized in terms of the concentration of percutaneous permeation enhancer and the loading dose of drugs.The pharmacokinetic behavior of the optimal formulation was studies in rabbits and the anti-inflammatory and analgesic effects of the optimal patch were evaluated with the adjuvant arthritis model in rats and the pain model in mice,respectively.The result showed that skin penetration of diclofenactriethylamine(DA-TEtA)salt was better than other organic amine salts.Based on previous study of our laboratory,teriflunomide-triethylamine(TEF-TEtA)significantly enhanced the skin permeation of TEF.10%of azone(AZ)was the best enhancer for the two drugs.The optimal patch formulation was composed of 2%of TEF-TEtA,6%of DA-TEtA and 10%of AZ.The cumulative permeated amount of DA-TEtA in vitro was comparable with that of the commercial diclofenac-diethylamine(DA-DEtA)patch.The absolute bioavailability of TEFTEtA was 42%,which could achieve the therapeutic drug levels.In animal study,the optimized compound patch containing DA-TEtA and TEF-TEtA displayed significant antiinflammatory and analgesic effect,which indicated the potential of the compound patch.

Polymethylmethacrylate Coated Alginate Matrix Microcapsules for Controlled Release of Diclofenac Sodium

Polymethylmethacrylate (PMMA) coated microcapsules of diclofenac sodium (DFS) were prepared by a modified wa-ter-in-oil-in-water (W1/O/W2) emulsion solvent evaporation method using sodium alginate (SAL) as a matrix material in the internal aqueous phase (W1).Their performance with respect to controlled release of the drug in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated, and compared with non-matrix microcapsules prepared by the conventional W1/O/W2 emulsion solvent evaporation method. Scanning electron micrographs (SEM) revealed that all the microcapsules were discrete and spherical in shape;however, the surface porosity of the matrix microcap-sules appeared to be less than that of the non-matrix microcapsules. In case of non-matrix microcapsules, an increase in the volume of water in W1 phase resulted in decrease in the drug entrapment efficiency (DEE) along with increase in release of the drug in both SGF and SIF. While in case of matrix microcapsules increase in the amount of SAL in W1 phase and concentration of the coating polymer in organic phase led to increase in DEE of the matrix microcapsules and considerable decrease in the drug release in both SGF and SIF. No interaction between the drug and any of the polymers used to prepare microcapsules was evident from Fourier transform infra-red (FTIR) analysis. The matrix microcapsules prepared using higher concentration of SAL and PMMA released the drug following zero order or Case-II transport model. The matrix microcapsules appeared to be suitable for releasing lesser amounts of DFS in SGF and providing extended release in SIF.

Study of diclofenac removal by the application of combined zero-valent iron and calcium peroxide nanoparticles in groundwater

Diclofenac(DCF)is one of the most frequently detected pharmaceuticals in groundwater,posing a great threat to the environment and human health due to its toxicity.To mitigate the DCF contamination,experiments on DCF degradation by the combined process of zero-valent iron nanoparticles(nZVI)and nano calcium peroxide(nCaO_(2))were performed.A batch experiment was conducted to examine the influence of the adding dosages of both nZVI and nCaO_(2)nanoparticles and pH value on the DCF removal.In the meantime,the continuous-flow experiment was done to explore the sustainability of the DCF degradation by jointly adding nZVI/nCaO_(2)nanoparticles in the reaction system.The results show that the nZVI/nCaO_(2)can effectively remove the DCF in the batch test with only 0.05 g/L nZVI and 0.2 g/L nCaO_(2)added,resulting in a removal rate of greater than 90%in a 2-hour reaction with an initial pH of 5.The degradation rate of DCF was positively correlated with the dosage of nCaO_(2),and negatively correlated with both nZVI dosage and the initial pH value.The order of significance of the three factors is identified as pH value>nZVI dosage>nCaO_(2)dosage.In the continuous-flow reaction system,the DCF removal rates remained above 75%within 150 minutes at the pH of 5,with the applied dosages of 0.5 g/L for nZVI and 1.0 g/L for nCaO_(2).These results provide a theoretical basis for the nZVI/nCaO_(2)application to remove DCF in groundwater.

Removal of diclofenac from aqueous solution with multi-walled carbon nanotubes modified by nitric acid

Modified multi-walled carbon nanotubes(MWCNTs) were used as adsorbents for removal of diclofenac. The reaction conditions were examined. Langmuir, Freundlich, Temkin, and Dubinin–Radushkevich isotherm models were applied to determine appropriate equilibrium expression. The results show that the experimental data fit the Freundlich equation well. Thermodynamic parameters show that the adsorption process is spontaneous and exothermic. The kinetic study indicates that the adsorption of diclofenac can be well described with the pseudo-second-order kinetic model and the process is controlled by multiple steps.

Structures, Lipophilicity, Dipole Moments, Acidity and Spectroscopic Properties of Non-Steroidal Anti-Inflammatory Drugs Diclofenac, Bromfenac and Amfenac: A Theoretical Study

This work is a contribution of theoretical chemistry to the classification of some non-steroidal anti-inflammatory drugs (NSAIDs). Indeed, research on the efficacy of NSAIDs has shown that no NSAID is recognized as the most efficient anti-inflammatory drug. We have made a theoretical study of diclofenac, bromfenac and amfenac, in order to compare their efficacy from some physicochemical properties. To do this, we used the DFT and TD-DTF methods at the B3LYP/6-311+G(d, p) level theory. The lipophilicity study shows that diclofenac and bromfenac are very lipophilic. Acidity study shows that diclofenac is more acid than bromfenac and amfenac. The results from molecular orbital and the TD-DFT calculations reveal that for the three NSAIDs, the lowest energy transition is due to the excitation from HOMO to LUMO. The absorption energy corresponding to H→L transition is comparable with the energy gap value. Our findings have shown that bromfenac is more reactive than amfenac, which is more reactive than diclofenac.

Determination of diclofenac in pharmaceutical preparations by voltammetry and gas chromatography methods

Rapid, sensitive and specific methods were developed for the determination of diclofenac in pharmaceutical preparations by linear sweep voltammetry （LSV） and gas chromatography （GC） with mass spectrometry （MS） detection. The linearity was established over the concentration range of 5- 35 μg/mL for LSV and 0.25-5 μg/mL for GC-MS method. The intra- and inter-day relative standard deviation （RSD） was less than 4.39% and 4.62% for LSV and GC-MS, respectively. Limits of quantification （LOQ） were determined as 4.8 and 0.15 μg/mL for LSV and GC-MS, respectively. No interference was found from tablet excipients at the selected assay conditions. The methods were applied for the quality control of commercial diclofenac dosage forms to quantify the drug and to check the formulation content uniformity.

Potentiometric determination of diclofenac in pharmaceutical formulation by membrane electrode based on ion associate with base dye

The characteristics, performance and application of membrane electrode based on ion associate of diclofenac with base dye Safranine T are described. The electrode response to diclofenac has the sensitivity of 47 ± 1.0 mV decade(?1) over the range of 5 × 10(?5) to 5 × 10(?2) mol/L at pH 6–12, and the detection limit of 3.2 × 10(?5) mol/L. The electrode is easy assembled at a relatively low cost has fast response time (2–4 s) and can be used for a period up to 3.5 months without any considerable divergence in potential. The proposed sensor displayed good selectivity for diclofenac in the presence of different substances. It was used to determine diclofenac in pharmaceuticals by means of the standard addition method.

A Proof-of-Concept Assessment of the Safety and Efficacy of Intralesional Diclofenac in the Treatment of Cutaneous Neurofibromas

The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective, safety and efficacy study of the effect of intralesionally administered diclofenac 25 mg/ml given once a week to 3 target cutaneous neurofibromas for 4 consecutive weeks. Overall, there was no significant change in neurofibroma size. During the study, some treated lesions developed signs of necrosis and fell off after a few weeks, but none of the control neurofibromas fell off. There were no significant changes in patient’s vital signs. A few adverse events occurred, mostly at the injection sites. During the study, some neurofibromas developed necrosis after the diclofenac injections and eventually detached from the patient. Overall, diclofenac was well tolerated, suggesting minimal systemic exposure, which required confirmation and further studies, including bioavailability analysis.