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 β-, hydroxyethyl-β-, and hydroxypropyl-β-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 β-cyclodextrin complex was polycrystalline, and the hydroxyethyl- and hydroxypropyl-β-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-β-cyclodextrin complexes were more soluble than the β-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 β- and hydroxyethyl-β-cyclodextrin complexes had superior dissolution when compared to the hydroxypropyl-β-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 β-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 β-cyclodextrin. No correlations were found among the bioavailability, solubility, and dissolution results.