The physicochemical characteristics and bioavailability of indomethacin from beta-cyclodextrin, hydroxyethyl-beta-cyclodextrin, and hydroxypropyl-beta-cyclodextrin complexes

Int J Pharm. 2004 Feb 11;270(1-2):149-66. doi: 10.1016/j.ijpharm.2003.10.012.


In an effort to improve the bioavailability of the insoluble drug indomethacin, three complexes were prepared with indomethacin and the soluble complexing agents beta-, hydroxyethyl-beta-, and hydroxypropyl-beta-cyclodextrin. The indomethacin content was similar among the complexes (P</=0.05). To confirm complex formation, each complex was characterized by ultraviolet, infrared, nuclear-magnetic resonance, powder X-ray diffraction, and differential-scanning calorimetry techniques. Powder diffraction studies show the beta-cyclodextrin complex was polycrystalline, and the hydroxyethyl- and hydroxypropyl-beta-cyclodextrin complexes were amorphous. Phase-solubility analysis confirmed the formation of complexes and suggested the three complexes were bound similarly. Solubility studies show complexation increased indomethacin solubility, and the hydroxyethyl- and hydroxypropyl-beta-cyclodextrin complexes were more soluble than the beta-cyclodextrin complex in 0.1 N hydrochloric acid and distilled water. Dosage forms were prepared by encapsulating the complexes without the addition of excipients. Dissolution studies show the encapsulated beta- and hydroxyethyl-beta-cyclodextrin complexes had superior dissolution when compared to the hydroxypropyl-beta-cyclodextrin and Indocin (50 mg) capsules. Bioavailability studies were performed by administering the indomethacin complex or Indocin capsules to male-albino, New Zealand rabbits. Indomethacin plasma-time concentration data fit best to a compartment-independent model for all capsule formulations. Bioavailability comparisons by ANOVA show no significant difference (P</=0.10) in the peak-plasma time and peak concentration among the capsule formulations. The area-under-the-curve for the beta-cyclodextrin complex capsules was found to be significantly higher (P</=0.10) than all other capsule formulations. In conclusion, the bioavailabilty of indomethacin was improved by complexation with only beta-cyclodextrin. No correlations were found among the bioavailability, solubility, and dissolution results.

Publication types

  • Comparative Study

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Administration, Oral
  • Ammonia / chemistry
  • Animals
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Capsules
  • Chromatography, High Pressure Liquid
  • Crystallization
  • Cyclodextrins / chemistry*
  • Hydrogen-Ion Concentration
  • Indomethacin / administration & dosage
  • Indomethacin / chemistry*
  • Indomethacin / pharmacokinetics
  • Magnetic Resonance Spectroscopy
  • Male
  • Rabbits
  • Solubility
  • Spectrophotometry, Infrared
  • Water / analysis
  • X-Ray Diffraction
  • beta-Cyclodextrins*


  • Capsules
  • Cyclodextrins
  • beta-Cyclodextrins
  • Water
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Ammonia
  • 2-hydroxyethyl-beta-cyclodextrin
  • betadex
  • Indomethacin