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AAPS PharmSciTech Feb 2021Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties,...
Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties, aceclofenac (ACE) was cocrystallized with dimethyl urea (DMU) in 1:2 molar ratio by dry and solvent assisted grinding. The cocrystals were characterized by ATR-FTIR, DSC, and PXRD, and their surface morphology was studied by SEM. There was enhancement in intrinsic dissolution rate (IDR) (~eight- and ~fivefold in cocrystals prepared by solvent assisted grinding (SAG) and solid state grinding (SSG), respectively, in 0.1 N HCl, pH 1.2) and similarly (~3.42-fold and ~1.20-fold in phosphate buffer, pH 7.4) as compared to pure drug. Additionally, mechanical properties were assessed by tabletability curves. The tensile strength of ACE was < 1 MPa in contrast to the cocrystal tensile strength (3.5 MPa) which was ~1.98 times higher at 6000 psi. The tablet formulation of cocrystal by direct compression displayed enhanced dissolution profile (~36% in 0.1 N HCl, pH 1.2, and ~100% in phosphate buffer, pH 7.4) in comparison to physical mixture (~ 30% and ~ 80%) and ACE (~18% and ~50%) after 60 min, respectively. Stability studies of cocrystal tablets for 3 months indicated a stable formulation. Pharmacokinetic studies were performed by using rabbit model. The AUC (37.87±1.3 μgh/ml) and C (6.94±2.94 μg/ml) of the selected cocrystal C1 prepared by SAG were significantly enhanced (p < 0.05) and were ~3.43 and ~1.63-fold higher than that of ACE. In conclusion, new cocrystal of ACE-DMU was successfully prepared with improved tabletability, in vitro and in vivo properties.
Topics: Animals; Crystallization; Diclofenac; Drug Liberation; Drug Stability; Female; Male; Rabbits; Tablets; Urea
PubMed: 33564940
DOI: 10.1208/s12249-021-01938-7 -
Journal of the Science of Food and... Aug 2024Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due...
BACKGROUND
Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g) and submitted to three culinary treatments (roasting, steaming and grilling).
RESULTS
The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion.
CONCLUSION
Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Topics: Diclofenac; Cooking; Animals; Digestion; Food Contamination; Seafood; Fishes; Bass; Humans; Water Pollutants, Chemical; Smegmamorpha; Models, Biological
PubMed: 38437521
DOI: 10.1002/jsfa.13430 -
Drug Delivery and Translational Research May 2023Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs...
Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.
Topics: Humans; Diclofenac; Skin Absorption; Administration, Cutaneous; Skin; Emulsions; Excipients
PubMed: 36525200
DOI: 10.1007/s13346-022-01267-7 -
Behavioural Pharmacology Dec 2022Pain is a major problem that burdens the health and economy of societies worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are over-the-counter medications that...
Preclinical comparison of antinociceptive effects between ibuprofen, diclofenac, naproxen, and acetaminophen on acid-stimulated body stretching and acid-depressed feeding behaviors in rats.
Pain is a major problem that burdens the health and economy of societies worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are over-the-counter medications that are widely indicated for mild to moderate pain conditions. Clinically, the selection of a medication among this class is mainly based according to both patient's and doctor's previous experiences. Herein, we studied differences in therapeutic efficacies among the most commonly prescribed NSAIDs and acetaminophen in inflammatory pain rat model. Body stretching and food consumption behaviors were assessed after intraperitoneal administration of lactic acid. Initially, different concentrations of lactic acid were evaluated in adult male rats in both behavioral models. Acid concentrations of 1.8 and 3.2% were selected to assess the effects of ibuprofen, diclofenac, naproxen, and acetaminophen in body stretching and feeding behaviors, respectively. In the feeding study, food restriction for 1-24 h prior to feeding studies was assessed at first, and 24 h was selected for further tests. Acetaminophen (100 mg/kg), diclofenac (10 mg/kg), ibuprofen (10-32 mg/kg), and naproxen (3.2-10 mg/kg) significantly decreased acid-stimulated body stretching. Likewise, acetaminophen (100 mg/kg), diclofenac (10 mg/kg), and ibuprofen (32 mg/kg) increased food consumption significantly after 3.2% lactic acid. There were no significant differences between different test drugs efficacies in both stretching and feeding behaviors. In conclusion, feeding behavior provides a good appraisal for pain and analgesic drugs in preclinical studies. There were comparable efficacies between all tested medications in both lactic acid-stimulated body stretching and -depressed feeding behaviors.
Topics: Male; Animals; Rats; Ibuprofen; Acetaminophen; Naproxen; Diclofenac; Anti-Inflammatory Agents, Non-Steroidal; Pain; Analgesics; Feeding Behavior; Lactic Acid
PubMed: 36256732
DOI: 10.1097/FBP.0000000000000704 -
Journal of Healthcare Engineering 2022To investigate the effects of different nonsteroidal anti-inflammatory drugs combined with platelet-rich plasma on inflammatory factor levels in patients with...
OBJECTIVE
To investigate the effects of different nonsteroidal anti-inflammatory drugs combined with platelet-rich plasma on inflammatory factor levels in patients with osteoarthritis.
METHODS
The clinic data of 120 patients with osteoarthritis who were treated in our hospital (June 2019-June 2021) were retrospectively reviewed. All the patients were given platelet-rich plasma. According to the different nonsteroidal anti-inflammatory drugs the patients received, they were equalized into diclofenac sodium group, celecoxib group, and iguratimod group, with 40 cases in each group. After treatment, the patients' clinical efficacy was compared and analyzed.
RESULTS
After treatment, the pain degrees of the patients in the three groups were gradually reduced. After 4 weeks and 8 weeks of treatment, the statistical differences in the scores of Visual Analogue Scale (VAS) were found among the three groups. Specifically, compared with the other two groups, the iguratimod group had remarkably lower VAS scores ( < 0.05) and the celecoxib group had signally lower VAS scores compared with the diclofenac sodium group ( < 0.05). After treatment, the inflammatory factor levels of interleukin-6 (IL-6), tumor necrosis factor- (TNF-), and high-sensitivity C-reactive protein (hs-CRP) in the diclofenac sodium group were observably higher compared with the celecoxib group ( < 0.05), and the inflammatory factor levels in the celecoxib group were remarkably higher compared with the iguratimod group ( < 0.05). Before treatment, no notable difference in the Lysholm scores was found among the three groups, and the patients' knee joint function was gradually improved after treatment. To be specific, after 4 and 8 weeks of treatment, the iguratimod group had observably higher Lysholm scores compared with the other two groups ( < 0.05), and the celecoxib group had signally higher Lysholm scores compared with the diclofenac sodium group ( < 0.05). The iguratimod group got markedly lower Western Ontario and McMaster Universities (WOMAC) score compared with the celecoxib group ( < 0.05); Compared with the diclofenac sodium group, the celecoxib group got remarkably lower WOMAC score ( < 0.05). During treatment, few patients suffered from mild gastrointestinal discomfort and hepatic dysfunction in the three groups, and no other severe adverse reactions were found. No statistical difference in the total incidence of adverse reactions among the three groups was observed ( > 0.05).
CONCLUSION
The combination of nonsteroidal anti-inflammatory drugs with platelet-rich plasma can further reduce the inflammatory reactions of the patients with osteoarthritis and improve their knee joint function. Significantly, the iguratimod, with high safety, has observably better effects on inhibiting inflammatory factors and improving knee joint function compared with diclofenac sodium and celecoxib.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Diclofenac; Humans; Osteoarthritis, Knee; Platelet-Rich Plasma; Retrospective Studies; Treatment Outcome
PubMed: 35399859
DOI: 10.1155/2022/1979892 -
Molecules (Basel, Switzerland) Jul 2023Diclofenac is the most prescribed nonsteroidal anti-inflammatory drug worldwide and is used to relieve pain and inflammation in inflammatory arthritis. Diclofenac is...
Diclofenac is the most prescribed nonsteroidal anti-inflammatory drug worldwide and is used to relieve pain and inflammation in inflammatory arthritis. Diclofenac is associated with serious adverse effects, even in regular-dose regimens. Drug delivery systems can overcome this issue by reducing adverse effects and optimizing their efficacy. This study evaluated the activity of lipid-core nanocapsules loaded with diclofenac (DIC-LNCs) in an experimental model of adjuvant-induced arthritis. The diclofenac nanoformulation was obtained via self-assembly. A stereological analysis approach was applied for the morphological quantification of the volume, density, and cellular profile count of the metatarsophalangeal joints of rats. Proinflammatory cytokines and biochemical profiles were also obtained. Our results showed that the diclofenac nanocapsule DIC-LNCs were able to reduce arthritis compared with the control group and the DIC group. DIC-LNCs efficiently reduced proinflammatory cytokines, C-reactive protein, and xanthine oxidase levels. Additionally, DIC-LNCs reduced the loss of synoviocytes and chondrocytes compared with the DIC ( < 0.05) and control groups ( < 0.05). These data suggest that DIC-LNCs have anti-arthritic activity and preserve joint components, making them promising for clinical use.
Topics: Rats; Animals; Diclofenac; Nanocapsules; Arthritis, Experimental; Lipids; Cytokines
PubMed: 37446881
DOI: 10.3390/molecules28135219 -
Environmental Technology Nov 2021In this study, peracetic acid (PAA) activated by Fe(II) was proposed to remove diclofenac (DCF) in polluted water. It was found that Fe(II)/PAA system could effectively...
In this study, peracetic acid (PAA) activated by Fe(II) was proposed to remove diclofenac (DCF) in polluted water. It was found that Fe(II)/PAA system could effectively remove DCF at neutral condition, which has a significant advantage over classical Fenton process. According to the result of scavenging experiment, both hydroxyl radical and peroxy radical were considered to be responsible for the degradation of DCF. The influence of several operational parameters including initial pH, Fe(II) dosage, PAA concentration and common water matrix on DCF removal were investigated. 80% DCF was removed at mild condition (pH 6-7) within 60 s, and its removal rate could be enhanced with the increase in Fe(II) dosage and PAA concentration. Presence of and natural organic matter (NOM) was proved to have a significantly negative impact on DCF degradation. Four probable degradation pathways of DCF were proposed based on the detected reaction products, including hydroxylation, C-N bond cleavage, decarboxylation and dehydrogenation.
Topics: Diclofenac; Ferrous Compounds; Oxidation-Reduction; Peracetic Acid; Water Pollutants, Chemical
PubMed: 32295490
DOI: 10.1080/09593330.2020.1756926 -
European Journal of Gastroenterology &... Jan 2023Nonsteroidal anti-inflammatory drugs and proton pump inhibitors are known to affect the diagnostics of gastrointestinal disorders. The aim of this study was to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIM
Nonsteroidal anti-inflammatory drugs and proton pump inhibitors are known to affect the diagnostics of gastrointestinal disorders. The aim of this study was to investigate to what extent omeprazole, diclofenac or co-administration of these affects faecal calprotectin levels and the normalisation interval after cessation.
METHODS
Participants received 20 mg omeprazole daily for 2 weeks in the first sequence, 50 mg oral diclofenac three times daily for 2 weeks in the second and co-administration of these for 2 weeks in the third, with washout periods in between. The first two sequences were randomised to a different order. Faecal calprotectin was measured on days 0, 4, 7, 14, 21, 28 and 35 and thereafter at 7-day intervals until normalisation in each sequence.
RESULTS
Thirty-two healthy volunteers were included. During drug intake, 39% on diclofenac (median 70.8 µg/g; range 50.2-1080 µg/g), 53% on omeprazole (median 85.3 µg/g; range 51.1-249 µg/g) and 69% on omeprazole + diclofenac (median 101.5 µg/g; range 51.5-532 µg/g) had faecal calprotectin levels above normal. In the diclofenac sequence, faecal calprotectin returned to normal in all participants within 2 weeks of cessation and in the omeprazole and co-administration sequences, within 3 weeks of cessation. No statistical significant difference was found with respect to drug order.
CONCLUSION
Short-term intake of omeprazole, diclofenac or co-administration appears to increase faecal calprotectin levels. In patients with increased faecal calprotectin on omeprazole alone or in combination with diclofenac, a repeated faecal calprotectin test is recommended at least 3 weeks after cessation. On diclofenac alone, it is sufficient to repeat the faecal calprotectin test 2 weeks after cessation.
Topics: Humans; Leukocyte L1 Antigen Complex; Omeprazole; Diclofenac; Feces; Proton Pump Inhibitors
PubMed: 36468569
DOI: 10.1097/MEG.0000000000002473 -
Science (New York, N.Y.) Sep 2021
Topics: Animals; Cattle; Conservation of Natural Resources; Diclofenac; Extinction, Biological; Raptors; Renal Insufficiency; Veterinary Drugs
PubMed: 34516815
DOI: 10.1126/science.acx9048 -
Journal of Nanobiotechnology Oct 2020Magnetic nanocomposites with a core-shell nanostructure have huge applications in different sciences especially in the release of the drugs, because of their exclusive...
BACKGROUND
Magnetic nanocomposites with a core-shell nanostructure have huge applications in different sciences especially in the release of the drugs, because of their exclusive physical and chemical properties. In this research, magnetic@layered double hydroxide multicore@shell nanostructure was synthesized by the facile experiment and is used as novel drug nanocarrier.
METHODS
Magnetic nanospheres were synthesized by a facile one-step solvothermal route, and then, layered double hydroxide nanoflakes were prepared on the magnetic nanospheres by coprecipitation experiment. The synthesized nanostructures were characterized by FTIR, XRD, SEM, VSM, and TEM, respectively. After intercalation with Ibuprofen and Diclofenac as anti-inflammatory drugs and using exchange anion experiment, the basal spacing of synthesized layered double hydroxides was compared with brucite nanosheets from 0.48 nm to 2.62 nm and 2.22 nm, respectively.
RESULTS
The results indicated that Ibuprofen and Diclofenac were successfully intercalated into the interlay space of LDHs via bridging bidentate interaction. In addition, in-vitro drug release experiments in pH 7.4, phosphate-buffered saline (PBS) showed constant release profiles with Ibuprofen and Diclofenac as model drugs with different lipophilicity, water solubility, size, and steric effect.
CONCLUSION
The FeO@LDH-ibuprofen and FeO@LDH-diclofenac had the advantage of the strong interaction between the carboxyl groups with higher trivalent cations by bridging bidentate, clarity, and high thermal stability. It is confirmed that FeO@LDH multicore-shell nanostructure may have potential application for constant drug delivery.
Topics: Animals; Anti-Inflammatory Agents; Delayed-Action Preparations; Diclofenac; Drug Carriers; Drug Compounding; Drug Liberation; Humans; Hydroxides; Ibuprofen; Intercalating Agents; Magnetic Iron Oxide Nanoparticles; Mice; Myoblasts; Nanocomposites; Particle Size; Solubility; Surface Properties
PubMed: 33121499
DOI: 10.1186/s12951-020-00718-y