Evaluation of cyclodextrin solubilization of drugs

Int J Pharm. 2005 Sep 30;302(1-2):18-28. doi: 10.1016/j.ijpharm.2005.05.042.

Abstract

The most common stoichiometry of drug/cyclodextrin complexes is 1:1, i.e. one drug molecule forms a complex with one cyclodextrin molecule, and the most common method for stoichiometric determination during formulation studies is the phase-solubility method. However, in recent years it has becoming increasingly clear that solubilizing effects of cyclodextrins are frequently due to the formation of multiple inclusion and non-inclusion complexes. The aqueous solubility of 38 different drugs was determined in pure aqueous solution, aqueous buffer solutions and aqueous cyclodextrin solutions, and the apparent stability constant (K1:1) of the 1:1 drug/cyclodextrin complexes calculated by the phase-solubility method. For poorly soluble drugs (aqueous solubility <0.1mM) the intrinsic solubility (S0) is in general much larger than the intercept of the phase-solubility diagram (Sint) resulting in non-linearity of otherwise linear (AL-type) phase-solubility diagram. This can lead to erroneous K(1:1)-values. A more accurate method for determination of the solubilizing efficiency of cyclodextrins is to determine their complexation efficiency (CE), i.e. the concentration ratio between cyclodextrin in a complex and free cyclodextrin. CE is calculated from the slope of the phase-solubility diagrams, it is independent of both S0 and Sint, and more reliable when the influences of different pharmaceutical excipients on the solubilization are being investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cyclodextrins / chemistry*
  • Drug Stability
  • Excipients / chemistry
  • Kinetics
  • Pharmaceutical Preparations / chemistry*
  • Solubility
  • Solutions / chemistry
  • Technology, Pharmaceutical / methods

Substances

  • Cyclodextrins
  • Excipients
  • Pharmaceutical Preparations
  • Solutions