Partitioning of ionizing molecules between aqueous buffers and phospholipid vesicles

J Pharm Sci. 1995 Oct;84(10):1180-3. doi: 10.1002/jps.2600841008.


The distribution of four ionizing molecules between small unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) and aqueous buffers has been studied as a function of pH using an ultrafiltration method. The results show that pH-distribution behavior observed in the standard 1-octanol-water system does not always apply in model membrane systems, since the charged form of some molecules are able to partition into a phospholipid bilayer. It was further shown that the partitioning of these charged species into the bilayer is not as a consequence of ion pairing. The results clarify reports suggesting that protonated amines have a surprisingly high membrane affinity, and the implications of these findings for drug design are discussed.

MeSH terms

  • Amlodipine / chemistry
  • Amlodipine / pharmacokinetics
  • Buffers
  • Chemical Phenomena
  • Chemistry, Physical
  • Dimyristoylphosphatidylcholine / chemistry*
  • Dimyristoylphosphatidylcholine / metabolism
  • Ions
  • Kinetics
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Membranes, Artificial*
  • Water / chemistry*
  • Water / metabolism


  • Buffers
  • Ions
  • Lipid Bilayers
  • Membranes, Artificial
  • Water
  • Amlodipine
  • Dimyristoylphosphatidylcholine