Diclofenac injectable

Online IS introduction allows loading of samples in the biological matrix without preparation. ISs were introduced online in the quantitation of propranolol and diclofenac in plasma (Alnouti et al. 2006). Plasma samples were loaded into the autosampler without pretreatment. Both the plasma sample (10 /iL) and IS (5 //I. from an IS microreservoir) were aspirated into an injection needle sequentially and injected into the sample loop. After the switching of an injection valve, the mixed solution in the sample loop was loaded into a cartridge containing washing solution for online SPE. The accuracy and precision of the online IS method were comparable (85 to 119% and 2 to 12%, respectively) to values obtained offline (86 to 106% and 2 to 16%, respectively). 

The first-line agents in the treatment of rheumatoid arthritis are non-steroidal anti-inflammatory drugs such as diclofenac. Diclofenac and indometacin, another NSAID, tend to have similar activity hov/ever, indometacin has a higher incidence of side-effects and therefore diclofenac is more appropriate for initial treatment. Sodium aurothiomalate is classified as a disease-modifying antirheumatic drug and is used as a second-line treatment in rheumatoid arthritis, but has been superseded by methotrexate, administered v/eekly. Paracetamol is often indicated in the management of osteoarthritis. Local intra-articular injections of dexamethasone may be administered for the relief of soft-tissue inflammatory conditions. 

Diclofenac is available as dispersible tablets, tablets, gel, suppositories and for intravenous or intramuscular injection. The maximum dose of diclofenac administered via any route is 150 mg. As v/ith other non-steroidal anti-inflammatory drugs, concomitant use in patients receiving venlafaxine increases the risk of bleeding. 

Figure 6.43 H spectrum of diclofenac glucuronide obtained after single trapping from a 100 pi injection of female urine 4 h after dosage of 50 mg of diclofenac. The spectrum was recorded using a cryogenic flow probe at 600 MHz. The spectrum indicates that the sensitivity is sufficient to run aU two-dimensional experiments needed for structure elucidation. Reproduced from [82] with permission from Elsevier.

Diclofenac is a phenylacetic acid derivative used mainly as sodium salt for the treatment of various pain and inflammation. Intramuscular injection occasionally causes tissue damage at the injection site. Suppositories may cause local irritation transient burning and stinging are reported when used for the eye and large doses can cause aplastic anemia.14... 

Nicolau syndrome (embolia cutis medicamentosa) is a very rare complication of intramuscular injections, in which there is extensive necrosis of the injected skin area, perhaps due to accidental intra-arterial and/or para-arterial injection it usually occurs in children (34). Of the NSAIDs with which it has been reported, diclofenac is the most common (35-38). 

Aseptic tissue necrosis after intramuscular injection (Nicolau syndrome) has been reported after accidental intra-arterial injection. Antirheumatic drugs are often involved in these reactions and diclofenac has also been implicated (42). Other consequences of intramuscular administration of diclofenac are asymptomatic high serum creatine kinase activity or damage to muscle, nerve, or blood vessels (SEDA-17,109). 

The adverse effects profile of suppositories, soluble tablet formulations, and standard capsules are similar (SEDA-13, 83). A parenteral formulation of piroxicam caused somnolence more often than diclofenac in a doubleblind study, but diclofenac provoked more gastric discomfort and nausea than piroxicam. Local adverse effects of both drugs were pain, burning, and induration at the site of injection (SEDA-15, 103). 

Macrogol 15 hydroxystearate is used in parenteral pharmaceutical preparations in concentrations up to 50% to solubilize diclofenac, propanidid, and vitamin Kl. It has also been used in preclinical formulations in preparing supersaturated injectable formulations of water-insoluble molecules. It is generally regarded as a relatively nontoxic and nonirritant excipient. 

Arthrotec misoprostol diclofenac, articaine [ban, inn) (carticaine) is an amide series local ANAESTHETIC, injected for dental and infiltration pain relief. Artracin indomethacin. 

Phenylacetic acid derivatives and related agents were introduced fairly recently. Those used therapeutically include diclofenac, ketorolac and tolmetin. They are reasonably well tolerated in use against skeletal muscle and joint pain. Diclofenac is sometimes used (by injection) for preoperative medication. Also, it is available in a preparation combined with a prostaglandin in an attempt to counteract its ulcerogenic effects (see ANTIULCEROGENIC AGENTS). 

Ortega-Barrales, P., Ruiz-Medina, A., Fernandez-De Cordova, M. L., and Molina Diaz, A. Sensitive and simple determination of diclofenac sodium by use of a continuous flow-injection procedure with solid-phase spectroscopic detection. Anal. Sci. 15(10) 985—989, 1999. 

Sintov et al. evaluated the pharmacokinetics of diclofenac from three formulations, viz. topical emulgel (Voltaren emulgel), topical microemulsion and subcutaneous injection... 

Figure 9.2 Pharmacokinetic profiles of diclofenac in rats after transdermal administration of Voltaren Emulgel and microemulsion compared to subcutaneous administration. The microemulsion formulation was superior to Voltaren Emulgel with respect to transdermal delivery and acted for longer time as compared to subcutaneous injection. (Figure redrawn with data from Ref. [59], reprinted with permission of Elsevier.)...

A.M. Pimenta, A.N. Araujo, M.C.B.S.M. Montenegro, Simultaneous potentiometric and fluorimetric determination of diclofenac in a sequential injection analysis system, Anal. Chim. Acta 470 (2002) 185. 

Opioid analgesics, e.g, morphine (Chapter 29), are rarely given before an operation unless the paiieni is in pain. Fentanyl and related drugs (e.g. alfcntanyh are used intravenou.sly to supplement nitrous oxide anaesthesia. These opioids are highly lipid soluble and have a rapid onset of action. They have a short duration of action because of redistribution. NSAIDs (e.g. diclofenac) may provide sufficient postoperative analgesia and do not cause respiratory depression. They can be given orally or by injection. 

Apart from the already established formulations, researchers are trying to develop novel oil-based formulations to combat the poor solubility and bioavailablity of NCE. Shevachman et al. developed novel U-type microemulsions to improve the percutaneous permeability of diclofenac. Shah et al.2 2 used microwave heating for the preparation of solid lipid nanoparticles by microemulsion techniques, which resulted in improved particle characteristics. Ki et al. reported sustained-release liquid crystal of injectable leuprolide using sorbitan monooleate. Recently, various novel oil-based drug delivery technologies are reported, which includes tocol emulsions, solid lipid nanopar-ticles, nanosuspensions, Upid microbubbles, sterically stabilized phospholipid micelles, and environmentally responsive drug delivery systems for parenteral administration.25 259... 

Diclofenac dates from the beginning of the 1970s, and was developed by Ciba-Geigy (now part of Novartis). It is marketed as its sodium or potassium salt in various formulations and dosage forms (injectable solutions, suppositories and capsules). 

A 52-year-old man developed skin necrosis after he tried to give himself an intramuscular injection of diclofenac 75 mg but actually injected the drug into an arterial perforator branch of the superficial femoral artery. 

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