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

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 less than or equal to 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 0.1N 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 Indocine (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 less than or equal to 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 less than or equal to 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. (C) 2003 Elsevier B.V. All rights reserved.