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British Journal of Clinical Pharmacology Jun 2011• Therapy with topical non-steroidal anti-inflammatory drugs (NSAIDs) relies on the ability of the active drug to penetrate the skin in sufficiently high amounts to... (Randomized Controlled Trial)
Randomized Controlled Trial
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Therapy with topical non-steroidal anti-inflammatory drugs (NSAIDs) relies on the ability of the active drug to penetrate the skin in sufficiently high amounts to exert a clinical effect, which is linked to the specific galenic properties of the formulation.
WHAT THIS STUDY ADDS
• This phase 1 study characterizes the transdermal penetration and plasma exposure of different dose levels with galenic differences of a novel topical diclofenac formulation under development and indicates greater diclofenac penetration through the skin when compared with a commercially available formulation.
AIMS
To evaluate the relative plasma and tissue availability of diclofenac after repeated topical administration of a novel diclofenac acid-based delivery system under development (DCF100C).
METHODS
This was a single-centre, open-label, three-period, crossover clinical trial of five discrete diclofenac formulations. Test preparations comprised two concentrations (1.0% and 2.5%) of DCF100C, with and without menthol and eucalyptus oil (total daily doses of 5 mg and 12.5 mg). Voltaren Emulgel gel (1.0%) was the commercially available comparator (total daily dose of 40 mg). Topical application was performed onto the thigh of 20 male healthy subjects for 3 days. Applying a Youden square design, each drug was evaluated in 12 subjects, with each subject receiving three test preparations. Blood sampling and in vivo microdialysis in subcutaneous adipose and skeletal muscle tissues were performed for 10 h after additional final doses on the morning of day 4.
RESULTS
All four DCF100C formulations demonstrated a three- to fivefold, dose-dependent increase in systemic diclofenac availability compared with Voltaren Emulgel and were approximately 30-40 times more effective at facilitating diclofenac penetration through the skin, taking different dose levels into account. Tissue concentrations were low and highly variable. The 2.5% DCF100C formulation without sensory excipients reached the highest tissue concentrations. AUC(0,10 h) was 2.71 times greater than for Voltaren Emulgel (90% CI 99.27, 737.46%). Mild erythema at the application site was the most frequent adverse event associated with DCF100C. There were no local symptoms after treatment with the reference formulation.
CONCLUSION
DCF100C formulations were safe and facilitated greater diclofenac penetration through the skin compared with the commercial comparator. DCF100C represents a promising alternative to oral and topical diclofenac treatments that warrants further development.
Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Cross-Over Studies; Diclofenac; Humans; Male; Skin Absorption; Statistics as Topic; Young Adult
PubMed: 21241352
DOI: 10.1111/j.1365-2125.2011.03914.x -
Journal of Pharmacy & Pharmaceutical... 2008There are evidences that glibenclamide, a sulfonylurea antidiabetic agent, reduces the analgesic action of non-steroidal antiinflammatory drugs (NSAIDs), opioids and...
PURPOSE
There are evidences that glibenclamide, a sulfonylurea antidiabetic agent, reduces the analgesic action of non-steroidal antiinflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. The purpose of this work was to examine in the rat if such interaction involves pharmacokinetic mechanisms or is solely limited to the pharmacodynamic level.
METHODS
All studies were carried out in female Wistar rats. Analgesia was assessed using the formalin test. Fifty microliters of diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection and a reduction in formalin-induced flinching was interpreted as an analgesic response. Rats were treated with oral diclofenac (3-18 mg/kg) in presence and the absence of oral glibenclamide (1-30 mg/kg). To evaluate the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (18 mg/kg) was studied in presence and the absence of glibenclamide (10 mg/kg).
RESULTS
Oral administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Coadministration of glibenclamide significantly reduced diclofenac-induced antinociception. Notwithstanding, the interaction does no appear to involve pharmacokinetic mechanisms, as oral glibenclamide failed to produce any significant alteration in oral diclofenac bioavailability.
CONCLUSION
Concomitant systemic administration of glibenclamide and diclofenac results in a reduction of the analgesic effect of the NSAID in the formalin test in the rat. This interaction, however, appears due solely to a pharmacodynamic mechanisms as diclofenac pharmacokinetics are not altered.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Diclofenac; Dose-Response Relationship, Drug; Drug Interactions; Female; Glyburide; Hypoglycemic Agents; Pain; Pain Measurement; Rats; Rats, Wistar
PubMed: 18801308
DOI: 10.18433/j3ks39 -
Drug Delivery Nov 2017The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFS) and DFS:Ion exchange resin complexes...
PURPOSE
The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFS) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively.
METHODS
Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFS, or a combination of DFS+DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. In vitro transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All in vivo studies were carried out as per the University of Mississippi IACUC approved protocol.
RESULTS
Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. In vitro transcorneal flux with the DFS+DFS:IR(1 + 1) was twice that of only DFS:IR film. In vivo, DFS solution and DFS:IR suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFS and DFS+DFS:IR(3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFS formulation.
CONCLUSION
DFS+DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.
Topics: Administration, Ophthalmic; Administration, Topical; Animals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diclofenac; Drug Delivery Systems; Eye; Ion Exchange Resins; Male; Ophthalmic Solutions; Organ Culture Techniques; Rabbits
PubMed: 28165833
DOI: 10.1080/10717544.2016.1256000 -
International Journal of Clinical... Oct 2010Acute pain caused by musculoskeletal disorders is very common and has a significant negative impact on quality-of-life and societal costs. Many types of acute pain have... (Review)
Review
Acute pain caused by musculoskeletal disorders is very common and has a significant negative impact on quality-of-life and societal costs. Many types of acute pain have been managed with traditional oral non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (coxibs). Data from prospective, randomised controlled clinical trials and postmarketing surveillance indicate that use of oral traditional NSAIDs and coxibs is associated with an elevated risk of developing gastrointestinal, renovascular and/or cardiovascular adverse events (AEs). Increasing awareness of the AEs associated with NSAID therapy, including coxibs, has led many physicians and patients to reconsider use of these drugs and look for alternative treatment options. Treatment with NSAIDs via the topical route of administration has been shown to provide clinically effective analgesia at the site of application while minimising systemic absorption. The anti-inflammatory and analgesic potency of the traditional oral NSAID diclofenac, along with its physicochemical properties, makes it well suited for topical delivery. Several topical formulations of diclofenac have been developed. A topical patch containing diclofenac epolamine 1.3% (DETP, FLECTOR(®) Patch), approved for use in Europe in 1993, has recently been approved for use in the United States and is indicated for the treatment of acute pain caused by minor strains, sprains and contusions. In this article, we review the available clinical trial data for this product in the treatment of pain caused by soft tissue injury.
Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Contusions; Diclofenac; Humans; Pain; Soft Tissue Injuries; Sprains and Strains; Transdermal Patch; Treatment Outcome
PubMed: 20666849
DOI: 10.1111/j.1742-1241.2010.02474.x -
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 -
The Journal of Toxicological Sciences Dec 2008Plasma protein binding is an important factor for the kinetics of drugs and how they act since it is the first step in drug distribution. Physiological changes in... (Comparative Study)
Comparative Study
Plasma protein binding is an important factor for the kinetics of drugs and how they act since it is the first step in drug distribution. Physiological changes in pregnancy, which include plasma composition, can affect drug binding and subsequent drug response. In the present study, we investigated the toxicokinetics (TK) and/or toxicodynamics (TD) of diclofenac and propranolol comparing pregnant Sparague-Dawley (SD) rats with non-pregnant SD rats in terms of protein binding and drug distribution. Diclofenac and propranolol are reported to bind to albumin and alpha(1)-acid glycoprotein (AGP), respectively. After a single administration of diclofenac, the area under plasma concentration-time curve (AUC) based on free diclofenac in pregnant rats was 3.9 times higher than that in non-pregnant rats. This difference is considered to be due to a lower concentration of serum albumin and a higher concentration of non-esterified fatty acid (NEFA) that inhibits drug binding to albumin, in pregnant rats. In histopathological examination, more severe gastrointestinal toxicity was observed in pregnant rats at 24 hr after dosing. This severe toxicity was likely to be correlated with the higher AUC. With respect to propranolol, the difference of the AUC based on free propranolol was not clear although the concentration of serum AGP was lower in pregnant rats. However, the binding analysis data suggested a difference of protein binding at a lower propranolol concentration range. Consequently, lowered serum proteins and increased NEFA in pregnant rats can lead to low protein binding, subsequent increase in free drug concentrations, and eventual increase in the TD of drugs.
Topics: Animals; Blood Proteins; Diclofenac; Female; Gastrointestinal Tract; Male; Metabolic Clearance Rate; Plasma Volume; Pregnancy; Propranolol; Protein Binding; Rats; Rats, Sprague-Dawley; Tissue Distribution; Toxicity Tests
PubMed: 19043274
DOI: 10.2131/jts.33.525 -
AAPS PharmSciTech Jul 2021An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the... (Review)
Review
An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel "solid-in-oil-in-water" (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient.
Topics: Diclofenac; Drug Carriers; Drug Stability; Emulsions; Microspheres; Nanostructures; Oils; Polylactic Acid-Polyglycolic Acid Copolymer; Proteins; Water
PubMed: 34212274
DOI: 10.1208/s12249-021-02074-y -
Anais Brasileiros de Dermatologia 2013Actinic keratosis is a frequent lesion which occurs in sunlight exposed areas. Diclofenac sodium and 5-Fluorouracil are effective, non-invasive and easy-to-apply topical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Actinic keratosis is a frequent lesion which occurs in sunlight exposed areas. Diclofenac sodium and 5-Fluorouracil are effective, non-invasive and easy-to-apply topical treatment options.
OBJECTIVES
To assess and compare the effectiveness of 3% diclofenac sodium associated with 2.5% hyaluronic acid and of 5% 5-Fluorouracil for the treatment of actinic keratosis, as well as the patient's degree of satisfaction and tolerability.
METHODS
28 patients with a clinical diagnosis of actinic keratosis were randomized to receive diclofenac sodium or 5-Fluorouracil and were clinically assessed before and after treatment as well as 8 weeks after the end of treatment. Modified versions of the Investigator and Patient Global Improvement Scores were used.
RESULTS
The average number of lesions in the diclofenac sodium group before and after treatment was 13.6 and 6.6 (p<0,001), respectively, while it was 17.4 and 3.15 (p<0.001) in the 5-Fluorouracil group. There was a significant reduction in the number of lesions in the 5-Fluorouracil group in relation to the diclofenac sodium group (p<0.001). To the non-blinded physician, there was a higher satisfactory therapeutic response in the 5-Fluorouracil group (p<0.001); to the blinded physician, there was a higher satisfactory response in this same group, although not statistically significant (p=0.09). There was a high degree of satisfaction in both groups (73% in the diclofenac sodium group and 77% in the 5-Fluorouracil group; p=0.827). Regarding adverse effects, the diclofenac sodium group presented a higher degree of satisfaction (93.3% vs 38.4%; p=0.008). Erythema, edema, crusts and itching were significantly higher in the 5-Fluorouracil group.
CONCLUSION
We concluded that 5-Fluorouracil was more effective; however, it showed lower tolerability than diclofenac sodium.
Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Chi-Square Distribution; Dermatologic Agents; Diclofenac; Female; Fluorouracil; Humans; Keratosis, Actinic; Male; Middle Aged; Patient Satisfaction; Time Factors; Treatment Outcome
PubMed: 24173178
DOI: 10.1590/abd1806-4841.20132083 -
Journal of Pain and Symptom Management Jan 2010Locally administered nonsteroidal anti-inflammatory drugs have been widely used in acute soft-tissue damage and articular musculoskeletal pain. This double-blind,... (Randomized Controlled Trial)
Randomized Controlled Trial
Locally administered nonsteroidal anti-inflammatory drugs have been widely used in acute soft-tissue damage and articular musculoskeletal pain. This double-blind, placebo-controlled, randomized study was designed to evaluate the efficacy and safety of a topical diclofenac sodium patch in the relief of pain and inflammation as a result of myofascial pain syndrome (MPS) in the upper trapezius. After sample size calculations indicated that 147 patients would be needed to detect a 25% difference between drug and control, 153 patients with MPS were recruited and randomized to receive either a diclofenac sodium patch or control (menthol) patch. Visual analog scale (VAS), cervical active range of motion, pressure pain threshold of the myofascial trigger point (MTrP), patient global assessment, Neck Disability Index, and the occurrence of adverse events were assessed on Day 0 (baseline), Day 4, and Day 8. Use of the diclofenac sodium patch elicited favorable responses for the VAS, cervical active range of motion, and Neck Disability Index by the end of the treatment course (P<0.05), and was consistently superior to the control patch at all time intervals. No significant differences were observed for the pressure pain threshold of the MTrP for either patch. Tolerability assessment similarly showed the diclofenac patch to be comparatively superior. When assessed at the end of the study, 20 diclofenac patch patients, but only four control patients, considered the tolerability of treatment to be "very good." Significant differences in adverse reactions were observed between the diclofenac and control patches, with the control patch more likely to produce overall skin irritation. This study demonstrate that the diclofenac sodium patch was superior to the control patch in terms of reducing pain and improving functional outcomes, and did not result in significant adverse effects.
Topics: Administration, Cutaneous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chi-Square Distribution; Diclofenac; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Myofascial Pain Syndromes; Severity of Illness Index; Treatment Outcome
PubMed: 19822404
DOI: 10.1016/j.jpainsymman.2009.05.016 -
Molecules (Basel, Switzerland) Apr 2020Caffeine and diclofenac are molecules with high human intake, and both belong to the 'emergent' class of contaminants. These compounds have been found at different...
Caffeine and diclofenac are molecules with high human intake, and both belong to the 'emergent' class of contaminants. These compounds have been found at different concentrations in many sources of water worldwide and have several negative impacts on aquatic life systems; that is why the search for new alternatives for their removal from aqueous media is of transcendental importance. In this sense, adsorption processes are an option to attack this problem and for this reason, biochar could be a good alternative. In this regard, were prepared six different biochar from fique bagasse (FB), a useless agroindustry by-product from fique processing. The six biochar preparations were characterized through several physicochemical procedures, while for the adsorption processes, pH, adsorption time and concentration of caffeine and diclofenac were evaluated. Results showed that the biochar obtained by pyrolysis at 850 °C and residence time of 3 h, labeled as FB850-3, was the material with the highest adsorbent capacity with values of 40.2 mg g and 5.40 mg g for caffeine and diclofenac, respectively. It was also shown that the experimental data from FB850-3 fitted very well the Redlich-Peterson isotherm model and followed a pseudo-first and pseudo-second-order kinetic for caffeine and diclofenac, respectively.
Topics: Adsorption; Caffeine; Cellulose; Charcoal; Chromatography, High Pressure Liquid; Diclofenac; Hydrogen-Ion Concentration; Kinetics; Solutions; Water Pollutants, Chemical
PubMed: 32316491
DOI: 10.3390/molecules25081849