Naproxen indications

Hirasawa and coworkers prepared a naproxen solid dispersion by melting, followed by rapid cooling with liquid nitrogen using lactose as a carrier. The dissolution studies of naproxen indicated that the dissolution rate was markedly increased in solid dispersions compared with physical mixtures and pure drugs. 

The determination of naproxen involved oscillometric titration (28) of its solution in aq. 20% acetone (10 ml, 10 mM in naproxen and containing 2 ml of aq. 0.1 M-NH3) with 0.1M-KOH, a Radelk is type OK-302 apparaturs being used for determining the end point. Results obtained for naproxen indicated the good precision of the oscillometric technique. 

Nano- The prefix on a metric unit indicating a multiple of 10-9,7 Naphthalene, 206t, 590 Naproxen, 601 Natural gas, 215,583 Natural logarithms, 645 Negative integer, 643 Neon, 32... 

Table 7.23 shows the results for 47 specific PAMPA models tested at pION, according the the scheme in Fig. 7.58. The two columns on the right are the r2 values in the comparisons. The neutral-lipid models (1.0, 1A.0, 2.0, 3.0, and 4.0) at pH 7.4 do not explain the permeability trend indicated in the human jejunal permeabilities [56]. Octanol was least effective, with r2 0.01. This should not be too surprising, since we did note that the appearance of naproxen, ketoprofen, and piroxicam at the top of the HJP ordering was unexpected. Our expectations were based on the octanol-water lipophilicity scale, which clearly does not correlate with the HJP trend. Adding a sink condition to the 2% DOPC model (model 1.1) improves correlation (r1 increases from 0.33 to 0.53). The addition of cholesterol to the 2% DOPC/dodecane system made the model unstable to the surfactant-created sink condition. 

Stuer et al. [46] evaluated the presence of the 25 most used pharmaceuticals in the primary health sector in Denmark (e.g., paracetamol, acetyl salicylic acid, diazepam, and ibuprofen). They compared PECs with experimental determinations and they conclude that measured concentrations were in general within a factor of 2-5 of PECs. Carballa et al. [45] also determined PECs for pharmaceuticals (17), musk fragrances (2) and hormones (2) in sewage sludge matrix. For that purpose they used three different approaches (1) extrapolation of the per capita use in Europe to the number of Spanish inhabitants for musk fragrances (2) annual prescription items multiplied by the average daily dose for pharmaceuticals and (3) excretion rates of different groups of population for hormones. They indicated that these PECs fitted with the measured values for half of them (carbamazepine, diazepam, ibuprofen, naproxen, diclofenac, sulfamethoxazole, roxithromycin, erythromycin, and 17a-ethiny I e strad iol). 

Nonsteroidal antiinflammatory drugs (NSAIDs) are the mainstay of therapy because of their excellent efficacy and minimal toxicity with shortterm use. There is little evidence to support one NSAID as more efficacious than another, and three drugs (indomethacin, naproxen, and sulindac) have FDA approval for this indication (Table 1-1). 

Other drugs are metabolised by Phase II synthetic reactions, catalysed typically by non-microsomal enzymes. Processes include acetylation, sulphation, glycine conjugation and methylation. Phase II reactions may be affected less frequently by ageing. Thus according to some studies, the elimination of isoniazid, rifampicin (rifampin), paracetamol (acetaminophen), valproic acid, salicylate, indomethacin, lorazepam, oxazepam, and temazepam is not altered with age. However, other studies have demonstrated a reduction in metabolism of lorazepam, paracetamol (acetaminophen), ketoprofen, naproxen, morphine, free valproic acid, and salicylate, indicating that the effect of age on conjugation reactions is variable. 

Considering the three solvent systems (1. 2 and 3) given in Table 13.3, indicate which set of Rf values is most likely to apply to naproxen. 

Naproxen is a naphthylpropionic acid derivative. It is the only NSAID presently marketed as a single enantiomer. Naproxen s free fraction is significantly higher in women than in men, but half-life is similar in both sexes (Table 36-1). Naproxen is effective for the usual rheumatologic indications and is available in a slow-release formulation, as an oral suspension, and over the counter. A topical preparation and an ophthalmic solution are also available. 

Clinical use Etodolac (Bellamy, 1997) is a drug, invented before the discovery of the COX isoenzymes. Thus, there was clinical experience with the drug, before it was shown, that etodolac has a 10-fold selectivity for COX-2 compared to COX-1 in human whole blood. Etodolac belongs to the first generation of COX-2 inhibitors (Vane et al., 1998). Clinical data indicate fewer gastrointestinal side-effects in comparison to naproxen (Taha et al., 1989 Bianchi Porro et al., 1991). Etodolac is a racemate with an active (S)-enantiomer and an inactive (R)-enantiomer. 

The solubility and release of naproxen from Pluronic PF-127 micelles were studied as a function of temperature and pH by Suh and Jun (1996). The solubility of the drug at pH 2 was signiLcantly increased as a linear function of PF-127 concentrations for three temperatures. Naproxen was highly entrapped by the micelles as indicated by large partition coefLcient. The micellar solubilization was a spontaneous (AG 0) and exothermic (AH< 0) process that resulted in a less ordered state (AS > 0). In the presence of PF-127, the release of naproxen was sustained at pH 2 and inversely proportional to the surfactant concentration. In contrast, at pH 7, PF-127 had little effect on the membrane transport of naproxen. The release of naproxen from the PF-127 gel into isopropanol myristate was also found to be dependent on the medium pH with the highest release observed at pH 6.3. 

The menstrual cycle is associated with two potentially incapacitating events dysmenorrhea and the premenstrual syndrome. Substantial evidence indicates that the excessive production of prostaglandin F2a is the major source of painful menstruation. The NSAIDs approved for the treatment of dysmenorrhea are aspirin, ibuprofen, mefenamic acid, and naproxen. 

Naproxen sodium tablets were used in an in vivo-in vitro evaluation with four different polymeric dispersions, cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), 50 50 CAP/CAT, and methacrylic acid copolymer [64], The study indicated that coating material that dissolves at a more acidic pH in vitro (such as CAT at pH 4.5) will also dissolve at a more acidic pH in vivo (i.e., the coating dissolves higher up in the GI tract). In addition, it was found that aging did not markedly affect dissolution characteristics of CAT or methacrylic acid copolymer-coated tablets. 

Rofecoxib is approved for the treatment of acute pain and dysmenorrhea at a dose of 50 mg for up to 5 days. The clinical studies indicate that rofecoxib shows efficacy similar to that produced by the maximum analgesic doses of naproxen and ibuprofen (Ehrich et al., 1999). The pain settings in which rofecoxib has been tested include acute postoperative dental pain, the pain of dysmenorrhea for up to 3 days, and postoperative pain for 5 days following surgical replacement of the knee or hip. In contrast, celecoxib is not approved in the United States for the treatment of acute pain, and it appears to be less effective when given acutely than rofecoxib, ibuprofen, or naproxen. The explanation for the differences between rofecoxib and celecoxib in acute pain is not known. 

This approach was studied for naproxen trifluoroethylthioester [55], feno-profen trifluoroethylthioester [56], naproxen trifluoroethylester [57] and ibupro-fen 2-ethoxyethyl ester [58] (Scheme 6.15). Some of these reactions were not performed in water only, but in biphasic mixtures, due to solubility problems. This is a drawback from a green point of view, but the much higher yield and the fact that no recycling step is needed is a clear indication of the high efficiency of dynamic kinetic resolutions. 

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