Selecting a non-interacting buffer for α-cyclodextrin containing solutions

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The article examines the effects of twelve pharmaceutically relevant buffers on the inclusion complex between α-cyclodextrin (α-CD) and 1,9-nonanediol using isothermal titration calorimetry. The key findings are:

  • Carboxylic acid-based buffers like fumaric acid, succinic acid, maleic acid, and malic acid demonstrated competitive binding with α-CD, significantly reducing its ability to complex 1,9-nonanediol. 
  • Phosphate, 2-morpholinoethanesulfonic acid (MES), Tris, and tartaric acid showed minimal interaction with α-CD, with complexation constants and thermodynamic properties similar to those observed in water. 
  • Complexation with hydroxypropylated α-cyclodextrin (HP-α-CD) consistently showed lower binding constants compared to α-CD, attributed to steric hindrance and increased cavity hydrophilicity. 
  • The findings highlight the importance of buffer selection in cyclodextrin-based drug formulations, as buffer-CD interactions are dependent on both buffer structure and CD cavity size. 
Illustration depicting various pharmaceutical buffers on the left, an α-cyclodextrin structure in the center, and an arrow leading to a representation of potential complexation with a pink interior.

Marlene Storm Andersen, Simon Løv Thomsen, Christian Schönbeck, René Holm (2025)
Selecting a non-interacting buffer for α-cyclodextrin containing solutions. International Journal of Pharmaceutics 683, 126049. https://doi.org/10.1016/j.ijpharm.2025.126049

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