Terfenadine-beta-cyclodextrin inclusion complex with antihistaminic activity enhancement

Terfenadine, an antihistaminic drug, has relatively low bioavailability aft er oral administration due to its limited solubility in water. To enhance t he antihistaminic activity of terfenadine, the terfenadine-beta -cyclodextr in (1:2) inclusion complex was prepared by the neutralization method. The s olubility and dissolution of the inclusion complex were carried out, and it s antihistaminic activity was then evaluated and compared with terfenadine powder by the passive subcutaneous anaphylaxis method in rats. The formatio n constant of the inclusion complex was higher at lower pH, while its forma tion ratio was 1:2 irrespective of pH. For terfenadine, it improved the sol ubility 200 times and the dissolution rate 5 times. It gave a low histamine level at 30 min, followed by a sustained low level until 60 min, while ter fenadine powder gave a low histamine level at 60 min, suggesting that it ha d faster and more effective antihistaminic activity than terfenadine powder in rats due to fast dissolution and absorption of terfenadine. It is concl uded that this inclusion complex enhanced the antihistaminic activity of te rfenadine following the enhanced solubility and dissolution of terfenadine.