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Accuracy of calcula...
Accuracy of calculated pH-dependent aqueous drug solubility.
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- Bergström, Christel A S (författare)
- Uppsala universitet,Institutionen för farmaci
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- Luthman, Kristina, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry
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- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- Engelska.
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Ingår i: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987. ; 22:5, s. 387-98
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Abstract
Ämnesord
Stäng
- The aim of the present study was to investigate the extent to which the Henderson-Hasselbalch (HH) relationship can be used to predict the pH-dependent aqueous solubility of cationic drugs. The pH-dependent solubility for 25 amines, carrying a single positive charge, was determined with a small-scale shake flask method. Each sample was prepared as a suspension in 150 mM phosphate buffer. The pH-dependent solubility curves were obtained using at least 10 different pH values. The intrinsic solubility, the solubility at the pKa and the solubility at pH values reflecting the pH of the bulk and acid microclimate in the human small intestine (pH 7.4 and 6.5, respectively) were determined for all compounds. The experimental study revealed a large diversity in slope, from -0.5 (celiprolol) to -8.6 (hydralazine) in the linear pH-dependent solubility interval, which is in sharp contrast to the slope of -1 assumed by the HH equation. In addition, a large variation in the range of solubility between the completely uncharged and completely charged drug species was observed. The range for disopyramide was only 1.1 log units, whereas that for amiodarone was greater than 6.3 log units, pointing at the compound specific response to counter-ion effects. In conclusion, the investigated cationic drugs displayed compound specific pH-dependent solubility profiles, indicating that that the HH equation in many cases will only give rough estimations of the pH-dependent solubility of drugs in divalent buffer systems.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Nyckelord
- Hydrogen-Ion Concentration
- Models
- Theoretical
- Pharmaceutical Preparations
- analysis
- chemistry
- Solubility
- Water
- analysis
- chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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