Naproxen sodium salt

The different forms mean that 275 mg naproxen sodium (salt of a weak acid) is equivalent to 250 mg of naproxen (free acid) and 550 mg is equivalent to 500 mg of naproxen. These products are not interchangeable however, they are considered pharmaceutical alternatives (see Ch. 7). 

Thus, [HRh(C0)(TPPTS)3]/H20/silica (TPPTS = sodium salt of tri(m-sulfophenyl)phopshine) catalyzes the hydroformylation of heavy and functionalized olefins,118-122 the selective hydrogenation of a,/3-unsaturated aldehydes,84 and the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic add (a precursor of naproxen).123,124 More recently, this methodology was tested for the palladium-catalyzed Trost Tsuji (allylic substitution) and Heck (olefin arylation) reactions.125-127... 

Naproxen is available as a free base, as sodium salt and in combination with misoprostol for the reduction of the gastrointestinal side-effects. 

The choline salts of naproxen and tolmetin yielded marked solubility enhancements, even over that of the sodium salts. The aqueous solubility of the choline salt of naproxen was 6700 times the solubility of naproxen and almost twice that of naproxen sodium. The choline salt of tolmetin was almost 8000 times as soluble as the parent drug and almost 5 times as soluble as its sodium salt (Murti, 1993) (Cheenu dissertation, our unpublished results). Table 15.2 shows that the melting points and enthalpies of fusion are both affected by the formation of the choline salt, and in fact, the choline salt proved to be more thermally stable. 

Since naproxen is a carboxylic acid, they chose to make the carboxyl ate salt of an enantio-merically pure amine, and found that the most effective was this glucose derivative. Crystals were formed, which consisted of the salt of the amine and (S)-naproxen, the salt of the amine with (f )-naproxen (the diastereoisomer of the crystalline salt) being more soluble and so remaining in solution. These crystals were filtered off and treated with base basic, releasing the amine (which can later be recovered and reused) and allowing the (S)-naproxen to crystallize as its sodium salt. 

Fig. 2 Solubility-pH profiles, 5x of naproxen and four salts A, potassium salt o, sodium salt , magnesium salt and V, calcium salt. (From Ref. l)...

Usually companies do not investigate other salt-forming species other than those shown in Table 3.8. However, Gu and Strickley (1987) have described the physical properties of the tris-(hydroxymethyl)aminomethane (THAM) salts of four analgesic/antiinflammatory agents with sodium salts and free acids. They concluded that the THAM salts had superior hygroscopicity properties compared to the sodium salts and did not show any loss in aqueous solubility or intrinsic dissolution rate. The one exception to this was the THAM salt of naproxen. Ketoralac is now marketed as the tromethamine or THAM salt. 

S)-(+) Naproxen sodium [2-Naphthaleneacetic acid, (+)-6-methoxy-a-methyl-, sodium salt] Active as an analgesic, antipyretic and anti-inflammatory... 

When administered as the acid or the sodium salt, naproxen is completely absorbed from the gastrointestinal tract the sodium sait is absorbed more rapidly than the acid (1). Peak plasma levels (about 55 (ig/ml) are reached in 2 to 4 hours after a 500 mg dose, and steady state ieveis are attained after 4-5 doses at 12 hours intervals. More than 99% is bound to serum albumin. The mean plasma half life is about 13 hours (2). Approximately 95% of a dose is excreted in the urine, principally as conjugates of naproxen and it s inactive metabolite 6-desmethyl naproxen (2). 

The usual dose of naproxen or naproxen sodium is the equivalent of 500 mg to 1 g of naproxen daily in 2 divided doses. A dose of 10 mg per kg body-weight daily of naproxens in 2 divided doses has been used in children over 5 years of age with juvenile rheumatoid arthritis (5). In painful conditions such as dysmenorrhoea the usual initial dose is the equivalent of 500 mg of naproxen followed by 250 mg every 6 or 8 hours. In accute gout an initial dose equivalent to 750 mg of naproxen followed by 250 mg every 8 hours has been suggested (5). Rectal administration of naproxen is sometimes employed naproxen has also been used orally as the piperazine salt (5). 

The 2-arylpropionic acid class (2-APA) of nonsteroidal anti-inflammatory drugs (NSAlDs) (Table 1) is characterized by each member having an asymmetric carbon a to the carboxylic acid moiety. The R-enantiomer of this chiral center of some 2-APAs may undergo an in vivo inversion to the S-enantiomer. This inversion process varies substantially between the different members of this class and also varies between species of animal studied. The members of this class that are currently in clinical use include ibuprofen, ketoprofen, tiaprofenic acid, fenoprofen, and flurbiprofen. The majority are marketed as racemates. Naproxen and its sodium salt are internationally marketed as the pure S(-l-)-enantiomer, while ibuprofen and ketoprofen are now marketed in several European countries as the stereochemically pure S(-l-)-enantiomer. 

Naproxen. Food did not have any clinically relevant effect on the pharmacokinetics of sustained-release naproxen in two studies. Taking a single 550-mg dose of naproxen sodium with a meal had no effect on its analgesic efficacy in postoperative pain, when compared with the fasted state. However, the rate of absorption of a single 550-mg dose of S-naproxen betainate sodium salt monohydrate was found to be reduced by a high-fat meal, when compared with the fasting state. ... 

One class of enzymes that has received particular attention in this regard is the esterases, which catalyze the hydrolysis of esters (Section 14.1C) to give an alcohol and a carboxylic acid. We illustrate this method by describing the resolution of (f ,5)-naproxen. The ethyl esters of both (R)- and (5)-naproxen are solids with very low solubilities in water. Chemists then use an esterase in alkaline solution to selectively hydrolyze the (S)-ester, which goes into the aqueous solution as the sodium salt of the (5)-carboxylic acid. The (fl)-ester is unaffected by these conditions. Filtering the alkaline solution recovers the crystals of the (i )-ester. After the crystals are removed, the alkaline solution is acidified to precipitate pure (5)-naproxen. The recovered (J )-ester can be racemized (converted to an f ,S-mixture) and again treated with the esterase. Thus, by recycling the (f )-ester, all the racemic ester is converted to (5)-naproxen. 

The sodium salt of (5)-naproxen is the active ingredient in Aleve and a score of other over-the-counter nonsteroidal anti-inflammatory preparations. 

The Food and Drug Administration has also approved two other drugs with similar structures to ibuprofen for over-the-counter use as pain relievers. These new drugs are known by their generic names, naproxen and ketoprofen. Naproxen is often administered in the form of its sodium salt. Naproxen and ketoprofen can be used to alleviate the pain of headaches, toothaches, muscle aches, backaches, arthritis, and menstrual cramps, and they can also be used to reduce fever. They appear to have a longer duration of action than the older analgesics. 

Notice in the structures shown above that the carboxylic acid, naproxen, has a plus sign of rotation while the sodium salt, sodium naproxen, has a minus sign of rotation when measured in a polarimeter. You should recall from your study of stereochemistry in your lecture course that a compound with (S) stereochemistry may have either a plus or a minus value in a polarimeter. Likewise, a compound with the (R) stereochemistry can have either a plus or minus value. 

In this experiment, you will be preparing the carboxylic acid, naproxen, rather than the sodium salt, sodium naproxen. As is often the case with pharmaceuticals. 

Obtain 10 mL of 3M aqueous HCl. Start adding it dropwise to the basic aqueous solution that contains the sodium salt of naproxen. Initially, the solution is heavily basic, and the naproxen is present as the sodium salt. As HCl is added, there will be localized formation of the white solid, naproxen. In that region, we have "neutralized" the solution. Using a stirring rod, mix the material so that the white solid redissolves. Overall, the solution is still basic. In effect we are using the appearance of the white solid as an indication of the end point. Think titration. Keep adding the HCl, dropwise, with stirring until the entire solution turns white (the end point ). At that point, check the pH to see if the solution is now acidic, about pH = 2. You may not use all of the HCl solution. Cool the mixture in an ice bath for 15 minutes. 

Naproxen is one of many drugs in the group classified as nonsteroidal anti-inflammatory drugs (NSAIDs). Naproxen is in the chemical class of propionic acid derivatives and possesses analgesic, antipyretic, and anti-inflammatory properties. It was first introduced in 1976 under the trade name Naprosyn by Roche Pharmaceuticals. Both the acid and salt formulations are currently used, with the salt form having a slightly more rapid absorption rate. Reduced-dose naproxen sodium was approved as an over-the-coimter (OTC) pain reliever in the USA in 1994 and entered the market under the trade name of Afleve [1,2]. 

Both naproxen and its sodium salt are rapidly absorbed in the gastrointestinal tract and are generally fully absorbed when taken orally. Peak plasma levels are obtained in 2-4 hours after ingestion of naproxen, and 1-2 hours after ingestion of the sodimn salt form (Anaprox ). The latter has significantly increased aqueous solubility. The enteric coated form of naproxen dissolves in the small intestine as opposed to the stomach therefore its absorption is delayed. 

Propose a liquid-liquid extraction (LLE) scheme to separate a sample containing naproxen sodium (an analgesic) and codeine as the hydrochloride salt. 

The anhydrous crystalline forms of Naproxen [(S)-(-l-)-2-(6-metho3gr-2-naphthyl)propionic acid], (NAPROA) and its sodium salt (NAPRO-S), widely used anti-inflammatory drugs, have been investigated by means of ID and 2D MAS NMR and DFT based calculations. From calculations, ID CP MAS and CRAMPS and 2D H- c MAS-J-HMQC, refocused INEPT, FSLG-HETCOR, and DQ-CRAMPS solid-state NMR experi-... 

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