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Journal of Pharmacy & Pharmaceutical... 2003Gastrointestinal (GI) side effects of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac may be reduced if it is administered as a complex with phospholipid. The... (Comparative Study)
Comparative Study
PURPOSE
Gastrointestinal (GI) side effects of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac may be reduced if it is administered as a complex with phospholipid. The upper and lower GI permeability induced by a diclofenac-dipalmitoyl phosphatidyl choline (DPPC) complex were compared with those of diclofenac acid and its sodium salt in rats.
METHODS
Pharmacokinetic studies were carried out to assess bioavailability of diclofenac preparations. Adult male Sprague-Dawley rats were dosed orally (equivalent to 15 mg/kg diclofenac sodium) as the acid or its sodium salt as well as diclofenac-DPPC complex. Upper and lower GI permeability, as surrogate markers of toxicity were determined using sucrose and 51Cr-EDTA, respectively.
RESULTS
At 1 h post-dose only diclofenac sodium induced a significant increased upper GI permeability. Three h post-dose all formulations significantly increased upper GI permeability although the diclofenac acid had the least effect. In the lower GI tract, the induced increase in permeability was significant at 1 and 3 h post-dose for all formulations with no significant differences between them.
CONCLUSION
The induced upper and lower GI toxicity of diclofenac was formulation and time dependent. The lack of effect of diclofenac acid was due to the decreased availability of the drug. In the upper GI tract, up to 1 h post-dose, the diclofenac-DPPC complex demonstrated reduced upper gastroduodenal permeability as measured by sucrose. However, the protective effect of DPPC did not last and was not extended to the lower GI tract due to the systemic effect, contribution from the enterohepatic recirculation and/or dissociation of the complex. In assessing diclofenac GI toxicity, the effect of the different formulations on the entire GI tract at various times after drug administration must be considered.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Diclofenac; Digestive System; Digestive System Physiological Phenomena; Male; Permeability; Phospholipids; Rats; Rats, Sprague-Dawley
PubMed: 14738716
DOI: No ID Found -
Drug Development and Industrial Pharmacy May 2003Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without...
Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.
Topics: Adhesiveness; Administration, Rectal; Animals; Chemical Precipitation; Diclofenac; Drug Compounding; Drug Stability; Gels; Hot Temperature; Intestinal Absorption; Intestinal Mucosa; Male; Poloxamer; Rabbits; Rats; Rats, Sprague-Dawley; Sodium Chloride; Suppositories; Time Factors
PubMed: 12779284
DOI: 10.1081/ddc-120018643 -
Nuclear Medicine and Biology Feb 2011The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in... (Clinical Trial)
Clinical Trial
The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. (11)C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Diclofenac; Feasibility Studies; Humans; Positron-Emission Tomography
PubMed: 21315273
DOI: 10.1016/j.nucmedbio.2010.08.005 -
International Journal of Pharmaceutics Sep 2003Poloxamer solutions prepared with poloxamers and sodium chloride were previously reported to undergo a phase transition to bioadhesive gels at body temperature. For the...
Poloxamer solutions prepared with poloxamers and sodium chloride were previously reported to undergo a phase transition to bioadhesive gels at body temperature. For the development of a thermosensitive diclofenac sodium-loaded poloxamer gel, here we investigated the effect of sodium chloride on the release, safety and rectal absorption in rats of diclofenac sodium delivered by the poloxamer gels. P 188 delayed the release rates of diclofenac sodium from poloxamer gels. However, sodium chloride showed no significant effect on the release rates of diclofenac sodium from poloxamer gels. Release mechanism analysis showed the release of diclofenac sodium was proportional to the time. The initial plasma concentrations of diclofenac sodium in the rectal formulation [diclofenac sodium/poloxamer 407 (P 407)/poloxamer 188 (P 188)/sodium chloride (2.5/15/17/0.8%)] were significantly higher compared with those in semi-solid suppository. Furthermore, it gave significantly faster Tmax of diclofenac sodium than did semi-solid suppository, indicating that the diclofenac sodium from poloxamer gel could be absorbed faster than that from semi-solid one in rats. It did not cause any morphological damage to the rectal tissues. These results suggested that poloxamer gel with sodium chloride could be a more effective and safe rectal delivery system of diclofenac sodium.
Topics: Absorption; Animals; Diclofenac; Drug Delivery Systems; Gels; Intestinal Mucosa; Male; Poloxamer; Rats; Rats, Sprague-Dawley; Sodium Chloride
PubMed: 12954185
DOI: 10.1016/s0378-5173(03)00362-4 -
Pakistan Journal of Pharmaceutical... Jan 2005Diclofenac sodium was administered as 50 mg tablets to four healthy male volunteers in a two-way randomized crossover study in which volunteers were either fasted or... (Randomized Controlled Trial)
Randomized Controlled Trial
Diclofenac sodium was administered as 50 mg tablets to four healthy male volunteers in a two-way randomized crossover study in which volunteers were either fasted or were given a standard breakfast immediately prior to dosing. Blood samples were obtained upto 9 hours period and drug concentration were determined by HPLC method. Besides a significantly delayed (at p > 0.1) peak in fed state; an increase in absorption rate constant was observed as the only significant (at p > 0.05) effect of food on biopharmaceutic characteristic of diclofenac sodium. However, the intrinsic absorption of diclofenac sodium is also fast and it is not being the rate limiting factor in the bioavailability of diclofenac sodium, its decrease upto about 18 minutes (0.31 +/- 0.05 hr) from 11 minutes (0.19 +/- 0.02 hr) produces a null difference as the net effect on bioavailability, particularly when the drug is to be used in multiple dosage regimen.
Topics: Administration, Oral; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Diclofenac; Fasting; Half-Life; Humans; Male; Postprandial Period; Time Factors
PubMed: 16431378
DOI: No ID Found -
Colloids and Surfaces. B, Biointerfaces Apr 2018Due to the well-know surfactant-like properties of diclofenac sodium (DS), vesicular systems consisting exclusively of DS, named diclosomes, were designed with the aim...
HYPOTHESIS
Due to the well-know surfactant-like properties of diclofenac sodium (DS), vesicular systems consisting exclusively of DS, named diclosomes, were designed with the aim to minimize or avoid the use of other excipients and to improve the formulation biocompatibility.
EXPERIMENTS
Diclosomes were designed and characterized in terms of dimensions, polydispersity index, ξ-potential, drug retained, stability as a function of storage time and ex-vivo percutaneous permeation profiles. Additionally, diclosomes were incorporated into gel dosage forms and their performance in terms of permeation enhancement were evaluated.
FINDINGS
DS was found to form nanosized vesicular systems, both alone and in presence of cholesterol. Increasing hydrophobicity (due to the presence of cholesterol) resulted in smaller vesicles, always spherical and homogeneous in shape. Permeation of DS from free solution was found to be lower respect to ones obtained for all diclosomal formulations, allowing these aggregates to be considered as percutaneous permeation enhancers. DS permeated from diclosomal gels was higher than that obtained with traditional niosomal gel, DS plain gel and commercial specialty Voltaren Emulgel 1%, while containing a considerably lower drug amount.
Topics: Administration, Cutaneous; Animals; Diclofenac; Drug Compounding; Hydrodynamics; Inventions; Liposomes; Particle Size; Rabbits; Skin Absorption; Surface-Active Agents
PubMed: 29413594
DOI: 10.1016/j.colsurfb.2018.01.030 -
Drug Intelligence & Clinical Pharmacy Nov 1988Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth... (Review)
Review
Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans
PubMed: 3069424
DOI: 10.1177/106002808802201102 -
Drug Design, Development and Therapy 2018Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of...
PURPOSE
Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of drugs for intra-articular indications. Our aim was to compare the anti-inflammatory and analgesic efficacy of EP-combined topical administration of diclofenac sodium hydrogel (50 mg mL in 230 µL volume) with that of an equivalent dose of oral (75 mg kg) and simple topical administration.
METHODS
Arthritis was induced with the injection of 2% λ-carrageenan and 4% kaolin into the right knee joints of male Sprague Dawley rats. EP was applied for 8 min with 900 V high-voltage pulses for 5 ms followed by a 20 ms break. Drug penetration into the synovial fluid and plasma was detected by high-performance liquid chromatography. Leukocyte-endothelial interactions were visualized by intravital videomicroscopy on the internal surface of the synovium. Inflammation-induced thermal and mechanical hyperalgesia reactions, knee joint edema, and inflammatory enzyme activities were assessed at 24 and 48 h after arthritis induction.
RESULTS
EP significantly increased the plasma level of diclofenac as compared with the topical controls 10 min after the 2% λ-carrageenan and 4% kaolin injection. Increased leukocyte-endothelial interactions were accompanied by joint inflammation, which was significantly reduced by oral and EP diclofenac (by 45% and by 30%, respectively) and only slightly ameliorated by simple topical diclofenac treatment (by 18%). The arthritis-related secondary hyperalgesic reactions were significantly ameliorated by oral and EP-enhanced topical diclofenac treatments. The knee cross-section area (which increased by 35%) was also reduced with both approaches. However, simple topical application did not influence the development of joint edema and secondary hyperalgesia.
CONCLUSION
The study provides evidence for the first time of the potent anti-inflammatory and analgesic effects of EP-enhanced topical diclofenac during arthritis. The therapeutic benefit provided by EP is comparable with that of oral diclofenac; EP is a useful alternative to conventional routes of administration.
Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Cell Communication; Cytokines; Diclofenac; Electrochemotherapy; Knee Joint; Male; Peroxidase; Rats; Rats, Sprague-Dawley
PubMed: 29983546
DOI: 10.2147/DDDT.S161703 -
Scandinavian Journal of Rheumatology.... 1978Diclofenac sodium (Voltaren) is a non-steroid anti-inflammatory agent of a new chemical structure, which is animal experiments shows a high degree of anti inflammatory,...
Diclofenac sodium (Voltaren) is a non-steroid anti-inflammatory agent of a new chemical structure, which is animal experiments shows a high degree of anti inflammatory, analgesic, and antipyretic activity in various pharmacological models. It inhibits prostaglandin biosynthesis in vitro and in vivo, and this inhibitory effect at least partly explains the mechanism of action of the preparation. In animal experiments diclofenac sodium is characterised by a broad therapeutic range. Also, its gastrointestinal tolerability is better than that of other highly effective non-steroid anti-inflammatory agents. Two of the metabolites produced during the biotransformation of diclofenac sodium in man are also biologically active. The activity of these two metabolites, however, is very much weaker than that of unchanged diclofenac sodium and is comparable to that of phenylbutazone.
Topics: Animals; Arthritis, Rheumatoid; Chemical Phenomena; Chemistry; Cyclooxygenase Inhibitors; Diclofenac; Drug Evaluation, Preclinical; Gastric Mucosa; Intestinal Mucosa; Lethal Dose 50; Mice; Phenylacetates; Rats
PubMed: 98835
DOI: 10.3109/03009747809097211 -
International Urology and Nephrology 1992The prostaglandin synthesis inhibitor diclofenac sodium was given as suppository in the treatment of primary nocturnal enuresis in 24 patients. The statistically... (Comparative Study)
Comparative Study
The prostaglandin synthesis inhibitor diclofenac sodium was given as suppository in the treatment of primary nocturnal enuresis in 24 patients. The statistically significant difference in response to diclofenac sodium and to placebo leads us to use diclofenac sodium in primary nocturnal enuresis.
Topics: Child; Diclofenac; Enuresis; Female; Humans; Male; Placebos; Suppositories
PubMed: 1624253
DOI: 10.1007/BF02549637