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BioMed Research International 2013The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and...
The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and transfersomes. The prepared formulations had been characterized for the loaded drug amount and vesicle size. The prepared vesicular systems were incorporated into 1% Carbopol 914 gel, and a survey of in vitro drug release and drug retention into rat skin has been done on them using a modified Franz diffusion cell. The cumulative amount of drug permeated after 24 h, flux, and permeability coefficient were assessed. Stability studies were performed for three months. The size of vesicles ranged from 145 to 202 nm, and the encapsulation efficiency of the Diclofenac sodium was obtained between 42.61% and 51.72%. The transfersomes and ethosomes provided a significantly higher amount of cumulative permeation, steady state flux, permeability coefficient, and residual drug into skin compared to the conventional liposomes, conventional gel, or hydroethanolic solution. The in vitro release data of all vesicular systems were well fit into Higuchi model (RSD > 0.99). Stability tests indicated that the vesicular formulations were stable over three months. Results revealed that both ethosome and transfersome formulations can act as drug reservoir in skin and extend the pharmacologic effects of Diclofenac sodium.
Topics: Administration, Cutaneous; Animals; Diclofenac; Drug Carriers; Liposomes; Male; Particle Size; Permeability; Rats; Skin
PubMed: 23936825
DOI: 10.1155/2013/616810 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Aug 2023To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then...
OBJECTIVE
To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and and biological properties.
METHODS
Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the "click chemistry" method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination.
RESULTS
The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (<0.05). experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (<0.05).
CONCLUSION
HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
Topics: Animals; Rats; Matrix Metalloproteinase 13; Microspheres; Hydrogels; Collagen Type II; Diclofenac; Inflammation; Osteoarthritis, Knee; Hyaluronic Acid; Aggrecans
PubMed: 37586790
DOI: 10.7507/1002-1892.202302105 -
Journal of Veterinary Science Jul 2022At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms...
BACKGROUND
At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous.
OBJECTIVES
This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens.
METHODS
Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10). DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology.
RESULTS
Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were "protein processing in endoplasmic reticulum," "retinol metabolism," and "glycine, serine, and threonine metabolism."
CONCLUSIONS
The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.
Topics: Animals; Chemical and Drug Induced Liver Injury; Chickens; Diclofenac; Mammals; Proteomics; Vitamin A
PubMed: 35698810
DOI: 10.4142/jvs.22018 -
Journal of Pharmaceutical Sciences Apr 2009Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR)...
Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Chemical Phenomena; Diclofenac; Excipients; Humans; Solubility; Tablets; Therapeutic Equivalency
PubMed: 18752289
DOI: 10.1002/jps.21525 -
Insight (American Society of Ophthalmic... Apr 1996Nonsteroidal antiinflammatory drugs have unique properties that aid the cataract surgeon. In phacoemulsification surgery, patients routinely receive nonsteroidal... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
Nonsteroidal antiinflammatory drugs have unique properties that aid the cataract surgeon. In phacoemulsification surgery, patients routinely receive nonsteroidal antiinflammatory drugs along with their dilating drops to inhibit intraoperative miosis. After surgery, these drugs can control inflammation and inhibit the development of cystoid macular edema. We present two prospective randomized studies. In the first, diclofenac sodium was compared with prednisolone acetate for control of postoperative inflammation. In the second, diclofenac sodium was compared with flurbiprofen for inhibition of intraoperative miosis. Diclofenac sodium was found to be as effective as prednisolone acetate for control of postoperative inflammation and as effective as flurbiprofen for inhibition of intraoperative miosis. Thus, whereas in the past we used a nonsteroidal antiinflammatory drug before surgery for inhibition of intraoperative miosis and a steroid drop in the postoperative period to control postsurgical inflammation, we now have equal efficacy using the same drug in the entire perioperative period.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cataract Extraction; Diclofenac; Flurbiprofen; Humans; Postoperative Care; Prednisolone; Premedication; Treatment Outcome
PubMed: 8826226
DOI: 10.1016/s1060-135x(96)90025-1 -
Acta Medica Indonesiana Jul 2016to evaluate the analgesic effect, the side effects and the safety of analgesics following endoscopic urological procedure. (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Pipemidic Acid, Phenazopyridine HCL and Sodium Diclofenac on Pain Perception Following Endoscopic Urological Surgery: Double-blinded Randomized-Controlled Trial.
AIM
to evaluate the analgesic effect, the side effects and the safety of analgesics following endoscopic urological procedure.
METHODS
eighty patients who underwent endoscopic urological surgery at Kardinah Hospital, Tegal from June to July 2015 were divided into four groups. The experimental group was administered analgesic for 4 days pipemidic acid (A) 400 mg bid, or phenazopyridine (B) 200 mg tid, or sodium diclofenac (C) 50 mg bid and the control (D) group was administered placebo tid for 4 days. The analgesic effects were assessed using Visual Analog Scale (VAS). Association between variables was assessed using Cramers V and Kruskall Wallis.
RESULTS
the endoscopic urological procedures consisted of 30 patients for URS, 6 patients for lithotripsy, 17 patients for TURP, 24 patients for removal JJ stent and 3 patients for cystoscopy. The mean age of group A, B, C and D (control) was 50.1 (13.7), 50.7 (14.8), 49.1 (13.4), and 49.6 (14.3) years, respectively, and follow-up period was 7 days. The VAS score in all experimental groups was less than control group on day 1 to 7 following endoscopic urological procedures (p<0.05). In the experimental group, there was no difference between groups B and C (p>0.05). Group A demonstrated a more favourable analgesic effect than B and C (p<0.05). No serious side effects were detected in any of the cases.
CONCLUSION
we conclude that oral analgesics are effective for pain relief following endoscopic urological surgery. Pipemidic acid was found to have a superior analgesic effect than phenazopyridine HCl and sodium diclofenac.
Topics: Anesthetics, Local; Anti-Infective Agents, Urinary; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Double-Blind Method; Endoscopy; Female; Humans; Male; Middle Aged; Pain Perception; Phenazopyridine; Pipemidic Acid; Prospective Studies; Urologic Surgical Procedures
PubMed: 27840352
DOI: No ID Found -
Drug Discoveries & Therapeutics Nov 2022The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical...
The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical characteristics of the tape formulation. A questionnaire for the assessment of comfort level and satisfaction with two brand-name (Naboal, Voltaren) and four generic tapes (Yutoku, Teikoku, Rakool, Towa) containing sodium diclofenac was developed and then applied to 12 healthy volunteers. Results showed that Voltaren was difficult to apply to the skin and easier to peel off the skin than Naboal (p < 0.01). Moreover, Rakool was easier to peel than Naboal (p < 0.05). The mechanically measured peeling force was associated with pain during peeling off (r = -0.65), and the measured value of bending rigidity was associated with ease of peeling off (r = -0.97). The knowledge obtained regarding the influence of pharmaceutical properties on the degree of satisfaction with and usability of different tape formulations may be useful for supporting the selection of generic tapes tailored to individual needs or pharmacist preferences, and thus improve treatment adherence and clinical outcomes.
Topics: Humans; Diclofenac; Patient Selection; Drugs, Generic; Surveys and Questionnaires; Pharmacists
PubMed: 36261340
DOI: 10.5582/ddt.2022.01071 -
PloS One 2022Staphylococcus aureus is an opportunistic pathogen that causes wide range of nosocomial and community-acquired infections which have spread worldwide leading to an...
BACKGROUND AND OBJECTIVES
Staphylococcus aureus is an opportunistic pathogen that causes wide range of nosocomial and community-acquired infections which have spread worldwide leading to an urgent need for developing effective anti-staphylococcal agents. Efflux is an important resistance mechanism that bacteria used to fight the antimicrobial action. This study aimed to investigate the efflux mechanism in S. aureus and assess diclofenac, domperidone, glyceryl trinitrate and metformin as potential efflux pump inhibitors that can be used in combination with antibiotics for treating topical infections caused by S. aureus.
MATERIALS AND METHODS
Efflux was detected qualitatively by the ethidium bromide Cart-Wheel method followed by investigating the presence of efflux genes by polymerase chain reaction. Twenty-six isolates were selected for further investigation of efflux by Cart-Wheel method in absence and presence of tested compounds followed by quantitative efflux assay. Furthermore, antibiotics minimum inhibitory concentrations in absence and presence of tested compounds were determined. The effects of tested drugs on expression levels of efflux genes norA, fexA and tetK were determined by quantitative real time-polymerase chain reaction.
RESULTS
Efflux was found in 65.3% of isolates, the prevalence of norA, tetK, fexA and msrA genes were 91.7%, 77.8%, 27.8% and 6.9%. Efflux assay revealed that tested drugs had potential efflux inhibitory activities, reduced the antibiotic's MICs and significantly decreased the relative expression of efflux genes.
CONCLUSION
Diclofenac sodium, domperidone and glyceryl trinitrate showed higher efflux inhibitory activities than verapamil and metformin. To our knowledge, this is the first report that shows that diclofenac sodium, glyceryl trinitrate and domperidone have efflux pump inhibitory activities against S. aureus.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Diclofenac; Domperidone; Humans; Metformin; Microbial Sensitivity Tests; Multidrug Resistance-Associated Proteins; Nitroglycerin; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35905077
DOI: 10.1371/journal.pone.0272417 -
Scientific Reports Oct 2023Investigation of a unique and fast method for the determination and separation of a mixture of three drugs viz., ciprofloxacin (CIP), Ibuprofen (IBU), and diclofenac...
Investigation of a unique and fast method for the determination and separation of a mixture of three drugs viz., ciprofloxacin (CIP), Ibuprofen (IBU), and diclofenac sodium (DIC) in actual samples of human plasma. Also, the technique was used to look at their pharmacokinetics study. Hydrocortisone was chosen as the internal standard (IS). The drugs were chromatographically separated using an Acquity ultra-performance liquid chromatography UPLC ® BEH C18 1.7 µm (2.1 × 150 mm) column with a mobile phase composed of acetonitrile: water (65:35, v/v) adjusted to pH 3 with diluted acetic acid. Plasma proteins were precipitated with acetonitrile. The separated drugs ranged from 0.3 to 10, 0.2-11, and 1-25 µg/mL for CIP, IBU, and DIC, respectively. Calibration curves were discovered to achieve linearity with acceptable correlation coefficients (0.99%). Examination of quality assurance samples showed exceptional precision and accuracy. Following the successful application of this improved technique to plasma samples, the pharmacokinetic characteristics of each selected drug were evaluated using (UPLC) with UV detection at 210 nm. Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEnness Calculator (AGREE). Separation was achieved in only 4-min analysis time. The method's validation agreed with the requirements of the FDA, and the results were sufficient.
Topics: Humans; Diclofenac; Ibuprofen; Chromatography, High Pressure Liquid; Ciprofloxacin; Tandem Mass Spectrometry; Reproducibility of Results; Acetonitriles
PubMed: 37848502
DOI: 10.1038/s41598-023-44846-5 -
American Journal of Veterinary Research Apr 2017OBJECTIVE To determine the plasma pharmacokinetics and safety of 1% diclofenac sodium cream applied topically to neonatal foals every 12 hours for 7 days. ANIMALS Twelve... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized, controlled clinical trial of safety and plasma concentrations of diclofenac in healthy neonatal foals after repeated topical application of 1% diclofenac sodium cream.
OBJECTIVE To determine the plasma pharmacokinetics and safety of 1% diclofenac sodium cream applied topically to neonatal foals every 12 hours for 7 days. ANIMALS Twelve 2- to 14-day old healthy Arabian and Arabian-pony cross neonatal foals. PROCEDURES A 1.27-cm strip of cream containing 7.3 mg of diclofenac sodium (n = 6 foals) or an equivalent amount of placebo cream (6 foals) was applied topically to a 5-cm square of shaved skin over the anterolateral aspect of the left tarsometatarsal region every 12 hours for 7 days. Physical examination, CBC, serum biochemistry, urinalysis, gastric endoscopy, and ultrasonographic examination of the kidneys and right dorsal colon were performed before and after cream application. Venous blood samples were collected at predefined intervals following application of the diclofenac cream, and plasma diclofenac concentrations were determined by liquid chromatography-mass spectrometry. RESULTS No foal developed any adverse effects attributed to diclofenac application, and no significant differences in values of evaluated variables were identified between treatment groups. Plasma diclofenac concentrations peaked rapidly following application of the diclofenac cream, reaching a maximum of < 1 ng/mL within 2 hours, and declined rapidly after application ceased. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of the 1% diclofenac sodium cream to foals as described appeared safe, and low plasma concentrations of diclofenac suggested minimal systemic absorption. Practitioners may consider use of this medication to treat focal areas of pain and inflammation in neonatal foals.
Topics: Absorption, Physiological; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Liquid; Diclofenac; Female; Horses; Humans; Male; Mass Spectrometry
PubMed: 28346003
DOI: 10.2460/ajvr.78.4.405