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Antimicrobial Preservatives in Cyclodextrin-Containing Drug Formulations.

Phatsawee Jansook1,2, Hákon Hrafn Sigurdsson3, Frédéric Pilotaz4

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PubMed
Summary

Cyclodextrins (CDs) often inactivate antimicrobial preservatives in pharmaceutical formulations. This review explains how CD complexation affects preservative activity based on chemical structures and properties.

Keywords:
antimicrobial efficacy enhancerantimicrobial preservativecyclodextrininactivation

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Formulation
  • Microbiology

Background:

  • Antimicrobial preservatives are crucial for multidose pharmaceutical formulations to prevent microbial contamination.
  • Many formulations contain poorly water-soluble drugs requiring solubilizing excipients like cyclodextrins (CDs).
  • Cyclodextrins can interfere with the efficacy of essential antimicrobial preservatives.

Purpose of the Study:

  • To elucidate the interaction mechanisms between cyclodextrins and common pharmaceutical preservatives.
  • To explain the varying susceptibility of different preservatives to cyclodextrin-induced inactivation.
  • To review strategies for mitigating preservative inactivation in drug formulations.

Main Methods:

  • Review of scientific literature on cyclodextrin-preservative interactions.
  • Analysis of physicochemical properties influencing complexation and inactivation.
  • Discussion of excipient strategies to counteract preservative inactivation.

Main Results:

  • Cyclodextrin complexation significantly reduces or abolishes the antimicrobial activity of many preservatives.
  • Inactivation is dependent on the chemical structure and properties of both the cyclodextrin and the preservative.
  • Both lipophilic and highly water-soluble preservatives can be susceptible to inactivation by cyclodextrins.

Conclusions:

  • Understanding cyclodextrin-preservative interactions is vital for developing stable and effective pharmaceutical formulations.
  • The chemical nature of preservatives dictates their vulnerability to inactivation by cyclodextrins.
  • Alternative excipients or formulation adjustments may be necessary to maintain preservative efficacy.