Diclofenac preparation

In the patient with contact lenses, it is advised not to use diclofenac preparations for ophthalamic treatment. Diclofenac also is contraindicated for intravenous administration in patients with renal impairment, hypovolemia, dehydration, asthma, or cerebrovascular bleeding. 

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). 

It is a well-known fact that a pharmaceutical substance can be prepared by adopting different routes of synthesis based upon the dynamic ongoing research in the field of organic-reaction-mechanisms. Relentless efforts are exerted vigorously by reputed research laboratories across the world to look for shorter routes of synthesis bearing in mind the cost-effectiveness of the final product. For instance diclofenac sodium (an NSAID) can be manufactured by two methods, one using a bromo compound as a starting material while the other is based on a non-bromo compound. Nevertheless, the latter product is more in demand because it is completely devoid of bromine residues in the final product. 

Oxazolidin-5-ones (11.110) are structurally related to oxazolidines, combining the motifs of a lactone and an O-Mannich base. These derivatives have already been discussed in Sect. 8.7.5. However, they serve here as a transition to [3,1 ]benzoxazepin-4-ones as an example of potential prodrugs. Thus, [3,l]benzoxazepin-4-one derivatives (11.111, R = H or Me, R = H, Me, Et, or Ph) were prepared from diclofenac (11.112) [137]. These prodrugs were stable for at least a few hours in simulated gastric juice, but, when administered to rats elicited an anti-inflammatory response comparable to that of diclofenac. One compound (11.111, R = Me, R = Et) was even more active than diclofenac without producing the gastric mucosal injury (ulcers) caused in all rats by diclofenac itself. Here again, there was no indication of whether the mechanism of hydrolysis is chemical or enzymatic. 

All chemicals were used as received. PDADMAC and PAMPS were obtained from Aldrich Chemical Co. (Milwaukee, WI). Diclofenac sodium, sodium sulfathiazole, labetalol HCl, propranolol HCl, verapamil HCl, and diltiazem HCl were purchased from Sigma Chemical (St. Louis, MO). Dextrose USP was obtained from Amend Co. (Irvinton, NJ). Water was distilled and deionized using a Nanopure purihcation system (Fischer Scientihc, Fair Lawn, NJ). Simulated intestinal fluid was prepared using a O.OIM phosphate buffer (sodium phosphate monobasic and potassium phosphate dibasic) at pH 7 and 5.5 with different amounts of NaCl to vary the ionic strength. Simulated gastric fluid (pH 1.5) was prepared with concentrated HCl with different amounts of NaCl to vary the ionic strength. 

Celecoxib, a non-steroidal anti-inflammatory drug, is a cyclo-oxygenase-2 selective inhibitor that is as effective as diclofenac and naproxen. It should be used for the shortest period required to control symptoms. Use is associated v/ith an increased risk of thrombotic events and the cyclo-oxygenase-2 selective inhibitors are contraindicated in cerebrovascular disease. Mobic is the proprietary preparation of meloxicam. 

Voltarol is a proprietary preparation of diclofenac. Diclofenac, like all the nonsteroidal anti-inflammatory drugs, may lead to bronchoconstriction (particularly when used systemically) and therefore must be used with caution in asthma. 

Concomitant administration of methotrexate and Voltarol, a proprietary preparation of diclofenac, a non-steroidal anti-inflammatory drug, may result in accumulation of methotrexate as its excretion is reduced. The use of diclofenac and diuretics such as bendroflumethiazide may increase the risk of nephrotoxicity. Concomitant use of alcohol and an angiotensin-converting enzyme inhibitor such as lisinopril (Zestril) may result in an enhanced hypotensive effect. Alcohol and the benzodiazepine diazepam (Valium) may result in enhanced sedation. 

Voltarol is a brand-name preparation for diclofenac (NSAID) and modified-release tablets are available in 75 mg and 100 mg strength. Nu-seals is a proprietary preparation of enteric-coated aspirin 75 mg. Fentanyl, co-codamol and Suboxone (buprenorphine and naloxone) consist of opioid drugs. 

Diclofenac Voltaren) is a phenylacetic acid derivative that is a potent inhibitor of COX and that has analgesic, antiinflammatory, and antipyretic effects. Its use is accompanied by side effects similar to those of other NSAIDs. Indications for the drug include rheumatoid arthritis, osteoarthritis, and ophthalmic inflammation (use of an ophthalmic preparation). 

A formulation containing an anti-inflammatory agent (diclofenac sodium), two inert matrices (ethylcellulose and polyvinyl chloride), a lubricant (magnesium stearate) and talc was optimized and prepared by a double compression process. 

Gastrointestinal ulceration may occur less frequently than with some other NSAIDs. A preparation combining diclofenac and misoprostol decreases upper gastrointestinal ulceration but may result in diarrhea. Another combination of diclofenac and omeprazole was also effective with respect to the prevention of recurrent bleeding, but renal adverse effects were common in high-risk patients. Diclofenac, 150 mg/d, appears to impair renal blood flow and glomerular filtration rate. Elevation of serum aminotransferases occurs more commonly with this drug than with other NSAIDs. 

A 0.1% ophthalmic preparation is recommended for prevention of postoperative ophthalmic inflammation and can be used after intraocular lens implantation and strabismus surgery. A topical gel containing 3% diclofenac is effective for solar keratoses. Diclofenac in rectal suppository form can be considered for preemptive analgesia and postoperative nausea. In Europe, diclofenac is also available as an oral mouthwash and for intramuscular administration. 

Ring-constrained analogues 37 of the anti-inflammatory drug, diclofenac, have been prepared by acid-catalyzed condensation of aldehydes (or ethylene ketals of ketones) with 36 (Equation 4) <1998MI201>. This reaction presumably proceeds via intramolecular nucleophilic attack by the carboxylic acid group on an iminium ion intermediate from condensation of the secondary amine. Interestingly, the compounds 37 showed comparable activities to diclofenac in the formalin-induced rat paw edema test. 

Morpholinoalkyl esters (see Figure 16.1 for chemical structures) ofthe potent nonsteroidal anti-inLammatory agent, diclofenac, were prepared and characterized regarding solubility and hydrolysis reaction rates (Tammara et al., 1994). The alkyl group provides a spacer between the carboxylic acid... 

R. T. Sane, R. S. Samant, and V. G. Nayak, High performance liquid chromatographic determination of diclofenac sodium from pharmaceutical preparation, Drug Dev. Ind. Pharm., 75 1307 (1987). 

U. M. Shindle, N. M. Tendolkar, and B. S. Desai, Smiultaneous determination of paracetamol and diclofenac sodium in pharmaceutical preparations by quantititative TLC, J. Planar Chromatogr., 7 50(1994). 

The similar method using nickel (II) instead of cobalt, cadmium and manganese was also investigated by Salem et al. [49] for the quantitative determination of flufenamic, mefenamic and tranexamic acids, furose-mide, diclofenac sodium and thiaprofenic acid. Statistical analysis of the results compared to assays used in pharmacopoeias and the Amax methods revealed equal precision and accuracy. Furthermore, the assays were also applied for the determination of these drugs in pharmaceutical preparations. 

Topical nonsteroidal anti-inflammatory drugs (NSAIDs), such as bromfenac, diclofenac, ketorolac, and nepafenac, have been advocated, but there is evidence that commercially available preparations do not appear effective in treating episcleritis. Topical flurbiprofen and ketorolac were foimd to be no more effective than placebo in treating episcleritis therefore, treatment modalities other than topical NSAIDs should be used. 

Dichloro-N-phenylanihne 59a that is used for the production of antiinflammatory drug Voltaren (Diclofenac) can be conveniently prepared through intermediates 57a and 58a, as indicated in Scheme 22. The synthesis can be carried out in one pot [39-42]. The same reaction scheme applies to the synthesis of 2-chloro-6-fluoro-N-(4-tolyl)anihne 59b, an intermediate... 

Diclofenac sodium is the active of a variety of different topical, mainly gel, preparations. These preparations are as photosensitive as aqueous solutions, which show a 30% decrease in content after one hour. The absorption of diclofenac up to about 330 nm requires the use of compounds absorbing in the UV region from 300 to 350 nm. 

Shinde et al. 1138] developed a simple, rapid and reliable HPTLC method for simultaneous identification and quantification of paracetamol and diclofenac sodium in pharmaceutical preparations. They performed chromatography on silica 60 F154 plates, and used ketorolac tromethamine as internal standard. 

Several NSAIDs have topical preparations, for example ibuprofen (Ibugel), diclofenac (Voltarol emulgel), piroxicam (Feldene gel) and ketoprofen (Oruvail gel). The objective is to produce therapeutic local concentrations without (undesirable) systemic... 

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