AAPS PharmSciTech

, Volume 14, Issue 2, pp 517–522 | Cite as

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

  • Grzegorz Garbacz
  • Bartosz Kołodziej
  • Mirko Koziolek
  • Werner Weitschies
  • Sandra Klein
Brief/Technical Note


The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of carbon dioxide (CO2) from the solution results in an uncontrolled increase of the pH. In order to maintain the pH on the desired level, either a CO2 loss must be completely avoided or the escaped CO2 has to be replaced by quantitative substitution, i.e. feeding the solution with the respective amount of gas, which re-acidifies the buffer after dissociation. The present work aimed at the development of a device enabling an automatic pH monitoring and regulation of hydrogen carbonate buffers during dissolution tests.

Key words

bicarbonate media hydrogen carbonate buffer modified release physiological buffers biorelevant dissolution 


  1. 1.
    Diakidou A et al. Characterization of the contents of ascending colon to which drugs are exposed after oral administration to healthy adults. Pharm Res. 2009;26(9):2141–51.CrossRefPubMedGoogle Scholar
  2. 2.
    Vertzoni M et al. Dissolution media simulating the intralumenal composition of the small intestine: physiological issues and practical aspects. J Pharm Pharmacol. 2004;56(4):453–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Kalantzi L et al. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm Res. 2006;23(1):165–76.CrossRefPubMedGoogle Scholar
  4. 4.
    McConnell EL, Fadda HM, Basit AW. Gut instincts: explorations in intestinal physiology and drug delivery. Int J Pharm. 2008;364(2):213–26.CrossRefPubMedGoogle Scholar
  5. 5.
    Persson EM et al. The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids. Pharm Res. 2005;22(12):2141–51.CrossRefPubMedGoogle Scholar
  6. 6.
    Repishti M et al. Human duodenal mucosal brush border Na(+)/H(+) exchangers NHE2 and NHE3 alter net bicarbonate movement. Am J Physiol Gastrointest Liver Physiol. 2001;281(1):G159–63.PubMedGoogle Scholar
  7. 7.
    Liu F et al. Evolution of a physiological pH 6.8 bicarbonate buffer system: application to the dissolution testing of enteric coated products. Eur J Pharm Biopharm. 2011;78(1):151–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Fadda HM et al. Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems. Int J Pharm. 2009;382(1–2):56–60.CrossRefPubMedGoogle Scholar
  9. 9.
    Bodmeier R et al. The influence of buffer species and strength on diltiazem HCl release from beads coated with the aqueous cationic polymer dispersions, Eudragit RS, RL 30D. Pharm Res. 1996;13(1):52–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Wagner K, McGinity J. Influence of chloride ion exchange on the permeability and drug release of Eudragit RS 30 D films. J Control Release. 2002;82(2–3):385–97.CrossRefPubMedGoogle Scholar
  11. 11.
    Wagner KG, Gruetzmann R. Anion-induced water flux as drug release mechanism through cationic Eudragit RS 30D film coatings. AAPS J. 2005;7(3):E668–77.CrossRefPubMedGoogle Scholar
  12. 12.
    Ibekwe VC et al. An investigation into the in vivo performance variability of pH responsive polymers for ileo-colonic drug delivery using gamma scintigraphy in humans. J Pharm Sci. 2006;95(12):2760–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Ibekwe VC et al. Interplay between intestinal pH, transit time and feed status on the in vivo performance of pH responsive ileo-colonic release systems. Pharm Res. 2008;25(8):1828–35.CrossRefPubMedGoogle Scholar
  14. 14.
    McNamara DP, Whitney KM, Goss SL. Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs. Pharm Res. 2003;20(10):1641–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Sheng JJ, McNamara DP, Amidon GL. Toward an in vivo dissolution methodology: a comparison of phosphate and bicarbonate buffers. Mol Pharm. 2009;6(1):29–39.CrossRefPubMedGoogle Scholar
  16. 16.
    Mooney KG et al. Dissolution kinetics of carboxylic acids I: effect of pH under unbuffered conditions. J Pharm Sci. 1981;70(1):13–22.CrossRefPubMedGoogle Scholar
  17. 17.
    Mooney KG et al. Dissolution kinetics of carboxylic acids II: effect of buffers. J Pharm Sci. 1981;70(1):22–32.CrossRefPubMedGoogle Scholar
  18. 18.
    Bai G et al. Hydrodynamic investigation of USP dissolution test apparatus II. J Pharm Sci. 2007;96(9):2327–49.CrossRefPubMedGoogle Scholar
  19. 19.
    Bai G, Wang Y, Armenante PM. Velocity profiles and shear strain rate variability in the USP Dissolution Testing Apparatus 2 at different impeller agitation speeds. Int J Pharm. 2011;403(1–2):1–14.CrossRefPubMedGoogle Scholar
  20. 20.
    Bai G, Armenante PM. Hydrodynamic, mass transfer, and dissolution effects induced by tablet location during dissolution testing. J Pharm Sci. 2009;98(4):1511–31.CrossRefPubMedGoogle Scholar
  21. 21.
    Kukura J, Baxter JL, Muzzio FJ. Shear distribution and variability in the USP Apparatus 2 under turbulent conditions. Int J Pharm. 2004;279(1–2):9–17.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Grzegorz Garbacz
    • 1
    • 2
  • Bartosz Kołodziej
    • 3
  • Mirko Koziolek
    • 2
  • Werner Weitschies
    • 2
  • Sandra Klein
    • 2
  1. 1.Physiolution GmbHGreifswaldGermany
  2. 2.Institute of Biopharmaceutics and Pharmaceutical Technology, Department of PharmacyUniversity of GreifswaldGreifswaldGermany
  3. 3.Institute of Low Temperature and Structure ResearchPolish Academy of Sciences in WrocławWrocławPoland

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