Dissociation constants, solubilities and dissolution rates of some selected nonsteroidal antiinflammatories

Herzfeldt, Claus-Dieter; Kümmel, Reiner

doi:10.3109/03639048309039887

Cited by 114 publications

(46 citation statements)

References 5 publications

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“…Bosch and co-workers [31] determined the pK a of ibuprofen in aqueous media through a combination of experiment and computation. Their estimate of 4.5 agrees well with the previous literature values [32][33][34][35]. Since ibuprofen is comigrating with DP7 at pH 6.5, our optimal conditions were anticipated to be found between pH 4.5 and 6.5.…”

Section: Dp7-ibuprofen Interactionssupporting

confidence: 81%

Complexation trends and binding constants between dextrin oligomers and small molecules as measured through affinity capillary electrophoresis

et al. 2003

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Quantitative aspects of a previously reported pre-equilibration affinity/capillary electrophoretic methodology (Hong, M., et al., Anal. Chem. 1998, 70, 3590-3597) were studied using fluorescently labeled oligosaccharides and analgesic drugs. Frontal analysis capillary electrophoresis (FA-CE) was investigated for these interaction systems. In order to fulfill certain FA requirements, the analysis conditions of the sugar-drug combinations had to be adjusted individually. Only after the establishment of these conditions, acceptable binding data (association constants) could be obtained. The constants are in the range of weak hydrogen bonding and are comparable to the constants that were independently obtained through 1H nuclear magnetic resonance (NMR) spectroscopy.

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Section: Dp7-ibuprofen Interactionssupporting

confidence: 81%

Complexation trends and binding constants between dextrin oligomers and small molecules as measured through affinity capillary electrophoresis

et al. 2003

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“…The minimum aqueous solubility of selected acidic NSAIDs (Table 1), determined in aqueous buffer at several pH units below the pKa value (Herzfeldt and Kummel 1983) correlates closely with the time-to-peak plasma con- Fig. 4.…”

Section: A Zapropazon Ementioning

confidence: 99%

“…Whilst the pKa value for the dissociation of the enolic moiety is reported as 6.3 (aqueous alcohol) (Herzfeldt and Kummel 1983), an exact value for the dissociation of the protonated 1,2,4-triazine nucleus is not yet available.…”

Section: Physico-chemicai Character Of Azapropazonementioning

confidence: 99%

“…An analysis of existing solubility data (Jacob unpublished data; Herzfeldt and Kummel 1983;Walker 1985) and spectrophotometric data (Sugiyama et al unpublished data; Jacob unpublished data) for azapropazone using methods described by Krebs and Speakman (1945) and Herzfeldt and Kummel (1983) indicates that protonation of the basic component occurs below about pH 4.0-5.0. Thus the ionisation equilibrium of azapropazone is best described by two macroscopic constants, pK~ = 6.3 and pKa < 5.0.…”

Section: Physico-chemicai Character Of Azapropazonementioning

confidence: 99%

“…Available physical data for azapropazone (Sugiyama et al unpublished data;Jacob unpublished data;Fenner and Mixich 1973;Herzfeldt and Kummel 1983;Walker 1985) clearly differentiate this compound from the classical acidic NSAID when in aqueous solution below pH 4.0. We feel that the significance of this behaviour has been missed by several workers who have studied this molecule -substantial evidence exists which clearly shows that the physico-chemical characteristics of an NSAID in an acid environment are an important determinant of its ability to damage the gastric mucosa (Graf et al 1975;Brune et al 1977a, b;Schweitzer and Brune 1977;Brune and Graf 1978;Rainsford 1978;Rainsford and Brune 1978;Brune et al 1979).…”

Section: Introductionmentioning

confidence: 99%

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The amphiprotic character of azapropazone and its relevance to the gastric mucosa

McCormack

Brune

1990

Arch Toxicol

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Since most non-steroidal anti-inflammatory drugs (NSAIDs) contain only one obvious ionisable group at physiological pH levels then they may be easily identified as having either acidic or basic character. Basic NSAIDs are simply non-acidic NSAIDs capable of accepting a proton within the physiological pH range. Within this range, however, a few NSAIDs contain two obvious ionisable groups, one acidic and the other basic. Such compounds should be described as amphiprotic, and include NSAIDs such as 4- and 5-amino substituted salicylic acids, niflumic acid, amfenac, WY 18251, and azapropazone. The aqueous ionisation equilibrium of such compounds is complex and is described by two macroscopic ionisation constants. Evidence has accumulated during the last decade to support the view that the pharmacokinetic behaviour of NSAIDs contributes not only decisively to their therapeutic effects but also to the type and incidence of their side-effects. A priori, using a physicochemical argument, certain amphiprotic NSAIDs should be better tolerated by the gastric mucosa than the classical acidic compound. Of those NSAIDs commercially available in the United Kingdom azapropazone remains the only one for which amphiprotic behaviour has been described. Following our examination of available data for azapropazone we conclude that the use of amphiprotic compounds represents a logical approach towards solving the problem of NSAID-induced gastric mucosal damage.

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Solubility

2012

Absorption and Drug Development

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Dissociation constants, solubilities and dissolution rates of some selected nonsteroidal antiinflammatories

Cited by 114 publications

References 5 publications

Complexation trends and binding constants between dextrin oligomers and small molecules as measured through affinity capillary electrophoresis

Complexation trends and binding constants between dextrin oligomers and small molecules as measured through affinity capillary electrophoresis

The amphiprotic character of azapropazone and its relevance to the gastric mucosa

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