Pharmaceuticals naproxen

The protein-polymer microcapsules can be obtained by supercritical anti-solvent techniques [8]. Homogeneous protein-polymer mixtures were contacted with supercritical carbon dioxide in order to produce microspheres with diameter ranging from 1 to 5 pm and containing around 80% of protein. Production of PLA microparticles containing insulin, lysozyme, and chemotrypsin is claimed. SAS crystallization of a pharmaceutical (naproxen) and a biodegradable poly(L-lactic acid) was reported [8]. The results from SAS studies showed very small spherical particles... 

Considerable advances in asymmetric hydroformylation, a process which, among other things, provides a potential route to enantiomericaHy pure biologically active compounds, have occurred. Of particular interest are preparations of nonsteroidal antiinflammatory (NSAI) pharmaceuticals such as Naproxen (8) and Ibuprofen (9), where the represents a chiral center. 

Lipase-catalyzed kinetic resolutions are often practical for the preparation of optically active pharmaceuticals (61). For example, suprofen [40828-46-4] (45), which is a nonsteroidal antiinflamatory dmg, can be resolved by Candida glindracea]i 2Lse in >95% ee at 49% conversion (61). Moreover, hpase-based processes for the resolution of naproxen [22204-53-1] and ibuprofen [15687-27-1] (61) have also been developed. 

Hydroformylation has been extensively studied since it produces optically active aldehydes which could be important precursors for pharmaceutical and fine chemical compounds. Thus, asymmetric hydroformylation of styrene (Scheme 27) is a model reaction for the synthesis of ibuprofen or naproxen. Phosphorus ligands were used for this reaction with excellent results, espe-... 

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). 

In order to determine more precisely the fate of pharmaceuticals during sludge treatment, different experiments have been conducted in controlled conditions. In continuous anaerobic reactors treating sludge spiked with pharmaceuticals, Carballa et al. [114] observed removals higher than 80% for naproxen, sulfamethoxazole, and roxithromycin, while 40% and 23% of ibuprofen and iopromide, respectively, were eliminated at both mesophilic (37°C) and thermophilic (55°C) temperatures. For diclofenac and diazepam, elimination of about 60% was observed in mesophilic conditions while in thermophilic conditions, 38% and 73% of these two compounds, respectively, were eliminated. In these experiments, the sludge retention time (15 or 30 days) did not seem to influence pharmaceutical removal... 

Asymmetric Hydroformylation of Vinylarenes a-Arylpropanals, the products of asymmetric hydroformylation of vinylarenes, serve as useful intermediates for pharmaceutical drugs. For example, (5)-2-arylpropanals can be oxidized to the corresponding (5)-2-arylpropanoic acids, such as (5)-ibuprofen (Ar = 4-isobutylphe-nyl), (5)-naproxen (Ar = 6-methoxynaphthalen-2-yl), and (5)-suprofen (Ar = 4-(2-thienylcarbonyl)phenyl) (see later in chapter. Scheme 4.4). Styrene is thus one of the most popular substrates used to test new catalyst systems. Representative ligands and their use as Pt or Rh complexes in the asymmetric hydroformylation are summarized in Figure 4.1 and Table 4.1. (See also Scheme 4.3.)... 

Bioactive compounds from Blumea gariepina salicin, salicylic acid, tenoxicam, ketorolac, piroxicam, tolmetin, naproxen, flurbiprofin, diclofenac, and ibuprofen in pharmaceutical formulations and biological samples ... 

Diclofenac has been identified as one of the major pharmaceuticals in the waters in Berlin (Germany) at median concentrations of 0.47 pgL (Ternes et al., 2002 Ferrari et al., 2003). Other analgesics such as naproxen, phenazone, codeine, indome-tacin, fenoprofen, ketoprofen, phenylbutazone, and propyphenazone have also been detected in sewage and surface water (Heberer and Adam, 2005 Boyd et al., 2005), although data about their occurrence in the environment are not extensive. The data presented in Figure 2.5 are not exhaustive but are rather intended to show the great diversity in concentrations of some of the key PPCPs in wastewater. 

Enanlioselective hydrogenation of a-aryl-substituted acrylic acids has extensively been studied because of the pharmaceutical importance of the saturated products. Anti-inflammatory (S)-naproxen with 97% ee is obtained by the high-pressure hydrogenation of 2-(6 -methoxy-naphth-2/-yl)acrylic acid by using Ru(OCOCH3)2[(S)-binap] [99]. The hydrogenation rate is... 

The effect of various surfactants, the cationics-eetyl trimethyl ammonium bromide (CTAB), and cetyl pyridinium chloride (CPC), the anionic-sodium lauryl sulfate (SLS), and the nonionic-polysorbate 80 (Tween 80), on the solubility and ionization constants of some sparingly soluble weak acids of pharmaceutical interest was studied (Gerakis et al., 1993). Benzoic acid (and its 3-methyl-, 3-nitro-, and 4-tert-butyl-derivatives), acetylsalicylic acid, naproxen, and iopanoic acid were chosen as model drugs. The cationics, CTAB and CPC, were found to considerably increase th< ionization constant of the weak acidS Ka ranged from-0.21 to-3.57), while the anionic, SLS, showed a negligible effect and the nonionic, Tween 80, generally decreased the ionization constants Solubility of the acids increased in aqueous micellar and in acidiLed micellar solutions. 

The sodium naproxen extended release formulation from Andrx Pharmaceuticals contains a portion of the drug for initial burst release and another portion in the form of a sustained release matrix. Plasma levels of the drug are detected within 30 minutes of dosing, with peak plasma levels occurring at about 5 hours after dosing. 

Diastereomeric crystallization is commonly used in the production of a number of pharmaceuticals, such as ampicillin, ethambutol, chloramphenicol, diltiazem, fosfomycin, and naproxen (136). 

Recent studies in the pharmaceutical field using MBR technology are related to optical resolution of racemic mixtures or esters synthesis. The kinetic resolution of (R,S)-naproxen methyl esters to produce (S)-naproxen in emulsion enzyme membrane reactors (E-EMRs) where emulsion is produced by crossflow membrane emulsification [38, 39], and of racemic ibuprofen ester [40] were developed. The esters synthesis, like for example butyl laurate, by a covalent attachment of Candida antarctica lipase B (CALB) onto a ceramic support previously coated by polymers was recently described [41]. An enzymatic membrane reactor based on the immobilization of lipase on a ceramic support was used to perform interesterification between castor oil triglycerides and methyl oleate, reducing the viscosity of the substrate by injecting supercritical CO2 [42],... 

Both naproxen and ibuprofen are chiral but, while both enantiomers of ibuprofen are effective painkillers, and the drug is sold as a racemic mixture (and anyway racemizes in the body) only the (S) enantiomer of naproxen has anti-inflammatory activity. When the American pharmaceutical company Syntex first marketed the drug they needed a way of resolving the racemic naproxen they synthesized in the laboratory,... 

These ketones are important intermediates in the synthesis of fragrances of the musk type, of UV absorbents and of pharmaceuticals such as paracetamol, ibuprofen, S-naproxen. Thus, in the processes of ibuprofen synthesis (9), the first classical step is the acetylation of isobutylbenzene with acetic anhydride in presence of HF (Hoechst process) or of A1C13 (Boots process) ... 

Recently, ee s of 85-90% have been obtained for the asymmetric hydrocyanation of 6-methoxy-2-vinyhiaphthalene using nickel complexes of chiral bidentate phosphinites derived from glucose (abbreviated PP, equation 12). This reaction is of great interest to the pharmaceutical industry because the (S) enantiomer of the product nitrile is a useful precursor for the widely marketed antiinflammatory dmg naproxen (equation 13). The same reaction can be applied to a number of other vinyl aromatic compounds, including the precursor for the antiinflammatory drug ibuprofen (6) however, the ee is not as high. 

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