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

Authors :
Jambhekar S
Casella R
Maher T
Source :
International journal of pharmaceutics [Int J Pharm] 2004 Feb 11; Vol. 270 (1-2), pp. 149-66.
Publication Year :
2004

Abstract

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.

Details

Language :
English
ISSN :
0378-5173
Volume :
270
Issue :
1-2
Database :
MEDLINE
Journal :
International journal of pharmaceutics
Publication Type :
Academic Journal
Accession number :
14726131
Full Text :
https://doi.org/10.1016/j.ijpharm.2003.10.012