Terfenadine-beta-Cyclodextrin inclusion complex with antihistaminic activity enhancement

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Terfenadine exhibits low oral bioavailability due to poor water solubility.
• Enhancing solubility and dissolution is crucial for improving antihistaminic drug efficacy.

Purpose of the Study:

• To prepare and characterize a terfenadine-beta-cyclodextrin (1:2) inclusion complex.
• To evaluate the impact of this complex on terfenadine's solubility, dissolution, and antihistaminic activity.

Main Methods:

• Preparation of the inclusion complex using the neutralization method.
• Solubility and dissolution studies of the complex.
• In vivo evaluation of antihistaminic activity via passive subcutaneous anaphylaxis in rats.

Main Results:

• The terfenadine-beta-cyclodextrin complex significantly increased terfenadine solubility by 200-fold and dissolution rate by 5-fold.
• The complex demonstrated faster and more sustained antihistaminic activity compared to terfenadine powder in rats.
• Complex formation constant was pH-dependent, with a 1:2 molar ratio observed.

Conclusions:

• The terfenadine-beta-cyclodextrin inclusion complex effectively enhances terfenadine's solubility and dissolution.
• This enhancement leads to improved and faster antihistaminic activity in vivo.
• Beta-cyclodextrin complexation is a viable strategy for optimizing terfenadine's therapeutic potential.