The effects of cyclodextrins on drug release from fatty suppository bases: II. In vivo observations

H.W. Frijlink, Anko Eissens, Adelbert Schoonen, C.F. Lerk

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The effects of cyclodextrin complexation on the absorption of drugs from fatty suppositories was evaluated in human volunteers. Three model drugs: diazepam, ibuprofen and prednisolone were used. When diazepam was complexed with γ-cyclcodextrin the drug release from the fatty suppositories was changed as compared with suppositories containing pure drug. After melting and spreading, the lipid insoluble complex particles dissolved in the aqueous rectal fluid. As a result of dilution and displacement of the drug from the complex by endogenous lipids, the dissolved complex dissociated. Approximately 25% of the free drug was absorbed fairly rapidly. Due to the high o/w partition coefficient of diazepam, a significant amount of the free drug in the rectal fluid diffused back into the lipid suppository base. The absorption of this latter fraction was not different from that of the pure drug. With ibuprofen it was demonstrated that complexation of drugs administered in high doses decreased the absorption. The suppository with the complex contained 1000 mg of solid substance. This large amount of solid particles behaved like a matrix preventing the spreading of the suppository and dissolution of the complex. The bioavailability of prednisolone from fatty suppositories was not increased by complexation with β-cyclodextrin, but the large variability in the absorption was reduced.
Original languageEnglish
Pages (from-to)183-187
Number of pages5
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3
Publication statusPublished - Sep-1991


  • beta cyclodextrin
  • diazepam
  • gamma cyclodextrin
  • witepsol h 15
  • adult
  • article
  • complex formation
  • dissolution
  • drug absorption
  • drug bioavailability
  • drug release
  • human
  • human experiment
  • male
  • normal human
  • rectal drug administration
  • suppository

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