Naproxen, properties

Other arylpropionic acids include naproxen, ketopro-fen and flurbiprofen. They share most of the properties of ibuprofen. The daily oral dose of ketoprofen is 50-150 mg, 150-200 mg for flurbiprofen and 250-1000 mg for naproxen. Whereas the plasma elimination half-life of ketoprofen and flurbiprofen are similar to that of ibuprofen (1.5-2.5 h and 2.4-4 h, respectively), naproxen is eliminated much more slowly with a half-life of 13-15 h. 

Considerable effort has been directed towards the catalytic addition of HCN to vinylarenes since this represents a route to 2-arylpropionic acids, well-known anti-inflammatory agents.75 High levels of asymmetric induction are required (R)-naproxen has undesirable properties associated with it and only the ([Pg.277]

The effects of added C02 on mass transfer properties and solubility were assessed in some detail for the catalytic asymmetric hydrogenation of 2-(6 -meth-oxy-2 -naphthyl) acrylic acid to (Sj-naproxen using Ru-(S)-BINAP-type catalysts in methanolic solution. The catalytic studies showed that a higher reaction rate was observed under a total C02/H2 pressure of ca. 100 bar (pH2 = 50bar) than under a pressure of 50 bar H2 alone. Upon further increase of the C02 pressure, the catalyst could be precipitated and solvent and product were removed, at least partly by supercritical extraction. Unfortunately, attempts to re-use the catalyst were hampered by its deactivation during the recycling process [11]. 

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory dmgs (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by hydroxycarbonylation [51,53] (several more listed in [52]). The carbonylation of styrene itself serves as a useful test reaction in order to learn the properties of new catalytic systems, such as activity, selectivity to acids, regioselectivity (1/b ratio) and enantioselectivity (e.e.) in the branched product. In aqueous or in aqueous/organic biphasic systems complexes of palladium were studied exclusively, and the results are summarized in Table 5.2. 

To enhance the removal of substances with high sorption properties, for example diclofenac (log = 2.7 and log A ow = 4.5. 8), ferric and aluminium salts may be added, increasing their removal rate to as much as 50-70% [66]. This strategy can also improve the removal of acidic compounds, for example naproxen, by ioiuc or chelating interactions [55]. 

No detectable amounts of naproxen or its lysine conjugates were found in the plasma after administration of the conjugate and it can be inferred that excretion into the urine is the crucial process which determines the elimination rate fi. The lack of diffusion into the bloodstream is a favourable property in relation to unwanted extra-renal effects. 

Naproxen (Naprosyn) also has pharmacological properties and clinical uses similar to those of ibuprofen. It exhibits approximately equal selectivity for COX-1 and COX-2 and is better tolerated than certain NSAIDs, such as indomethacin. Adverse reactions related to the GI tract occur in about 14% of all patients, and severe GI bleeding has been reported. CNS complaints (headache, dizziness, drowsiness), dermatological effects (pruritus, skin eruptions, echinoses), tinnitus, edema, and dyspnea also occur. 

Its properties are very similar to those of other NSAIDs, though it may be less damaging to the stomach than some other NSAIDs when given at a dosage of 1000 mg/d. Unfortunately, higher dosages (eg, 1500-2000 mg/d) are often needed, and this is a very expensive NSAID. Like naproxen, nabumetone has been reported to cause pseudoporphyria and photosensitivity in some patients. Other adverse effects mirror those of other NSAIDs. 

Our group pursued another approach of combining the properties of nanoparticles with chiral nematic liquid crystal phases. The idea was to decorate gold nanoparticles with chiral molecules known to be strong inducers of chiral nematic phases. To realize the idea, we prepared a series of alkylthiol-capped gold nanoparticles, either pure monolayer or mixed monolayer, with all or about every second of the alkylthiols end-functionalized with (5)-naproxen (e.g., 6 in Fig. 11) [349]. 

Mura, P, Bettinetti, G. P, Cirri, M., Maestrelli, F., Sorrenti, M., and Catenacci, L. 2005. Solid-state characterization and dissolution properties of naproxen-arginine-hydroxyptjbtnylelodextrin ternary system. 

Thermal Properties and Aqueous Solubilities of Naproxen, Tolmetin, and Their Salts3... 

The enteric protection properties of a methacrylate polymer were investigated with the use of naproxen tablets [56] enteric coated with an aqueous dispersion of methacrylic acid copolymer (EUDRAGIT L 30 D-55, USP NF type C). 

Analytical Properties Separation of the drugs ibuprofen, ketoprofen, naproxen, 2-phenoxypropionic acid, bendroflumethiazide, ethotoin, hexobarbital, disopyramide, and RAC 109 retention and selectivity of the solutes can be regulated by addition of the tertiary amine /V,/V-dimethyloctylamine (DMOA) to the mobile phase DMOA decreases retention time and the enantioselectivity of the weaker acids but has opposite effects on the stronger acids Reference 3... 

RajanBabu and Casalnuovo [19, 20] tested diphosphinite ligand systems (5 and 6 in Figure 4) based on carbohydrate backbones. The steric and electronic properties depended on the substituents on the aryl groups on the phosphorus atoms. The use of different chlorophosphine precursors led to the electronically asymmetric ligand 6. This approach resulted in both enantiomers of naproxen nitrile from MVN in 91 % ee (S)-nitrile (ligand 5) and 95 % ee (R)-nitrile (ligand 6) at 0 °C. 

Dahl,T. C., Calderwood,T., Bormeth, A.,Trimble, K., and Piepmeier, E. (1990), Influence of physicochemical properties of hydroxypropyl methyl cellulose on naproxen release from sustained release matrix tablets, J. Controlled Release, 14,1-10. 

S)-Naproxen is the aaive ingredient in the widely used pain relievers Naprosyn and Aleve. The three-dimensional orientation of two atoms at a single carbon in naproxen determines its therapeutic properties. Changing the position of these two atoms converts this anti-inflammatory agent into a liver toxin. In Chapter 5 we learn more about stereochemistry and how small structural differences can have a large effect on the properties of a molecule. 

How differences in the three-dimensional structure of starch and cellulose affect their shape and function (Section 5.1) The three-dimensional structure of thalidomide, the anti-nausea dmg that caused catastrophic birth defects (Section 5.5) How mirror image isomers can have drastically different properties— the analgesic ibuprofen, the antidepressant fluoxetine, and the anti-inflammatory agent naproxen (Section 5.13)... 

Donato, L., Figoli, A., and Drioh, E., Novel composite poly(4-vinylpyridine)/polypropylene membranes with recognition properties for (S)-naproxen, J. Pharm. Biomed. Anal., 37, 1003, 2005. 

Katzhendler, I. Mader, K. Friedman, M. Structure and hydration properties of hydroxypropyl methylcellulose matrices containing naproxen and naproxen sodium. Int. J. Pharm. 2000, 200, 161-179. 

In a similar study, Mamdani et al. conducted a retrospective cohort study from 1998- 2001 with NSAID naive elderly patients who had either celecoxib, ro-fecoxib, naproxen, or other non-naproxen NSAIDs. [155] Prior to adjusting compared to the community group there was a significant increased risk of AMIs for all NSAIDs except naproxen which only trended towards an increase. But once the values were adjusted for comparison to their controls none of the groups had an increased risk that was significantly different than the controls. This study was designed to determine if naproxen had would decrease the risk of AMIs and they concluded that naproxen has no cardioprotective properties. This study also showed an increased risk of AMI for high dose ibuprofen. 

Propionic acid propanoic acid) derivatives have been extensively developed since the original introduction of ibuprofen into clinical use. Other examples of those in clinical use include fenbufen, flurbiprofen, ketoprofen, naproxen and oxaprozin. Many of these agents have a relatively low incidence of reported side-effects, however, their usage varies. Ibuprofen is the first analgesic since paracetamol to be licensed in the UK for non-prescription use but such use is limited to the treatment of relatively minor pain states, even though it has fair antiinflammatory properties. Most other members are reserved for systemic use to treat rheumatoid and osteoarthritis, musculoskeletal pain and similar states (some applied topically). 

In wet granulation, the quantity of solvent, usually water, has a definite influence on the tablet properties. Increasing the amount of water as granulation liquid gave naproxen tablets with a significantly higher dissolution rate [534], ace-... 

Haginaka,)., Sanbe, H. Uniformly sized molecularly imprinted polymer for (S)-naproxen. Retention and molecular recognition properties in aqueous mobile phase,/. Chromatogr. A, 2001, 913, 141-146. 

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