Dissolution properties and characterization of halofantrine-2-hydroxypropyl-beta-cyclodextrin binary systems

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Medicinal Chemistry

Background:

• Halofantrine (HF) is an antimalarial drug with poor water solubility and low bioavailability.
• Improving HF solubility and dissolution is crucial for enhancing its therapeutic efficacy.

Purpose of the Study:

• To investigate the complexation of halofantrine hydrochloride (HF.HCl) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD).
• To evaluate the impact of complexation on HF.HCl solubility, dissolution rate, and preparation methods.

Main Methods:

• Phase-solubility studies were conducted to determine the complexation behavior.
• Solid inclusion complexes were prepared using physical mixture, kneading, co-evaporation, and freeze-drying.
• Complexes were characterized using X-ray diffraction and Infra-red spectroscopy.
• Solubility and dissolution rates of HF.HCl from complexes were assessed.

Main Results:

• HP-beta-CD significantly increased HF solubility, forming 1:1 inclusion complexes with a stability constant of 2300 M⁻¹.
• Complex formation markedly enhanced the dissolution rate of HF.HCl.
• The freeze-drying method produced complexes with superior dissolution properties compared to other methods.

Conclusions:

• Complexation of HF.HCl with HP-beta-CD effectively improves drug solubility and dissolution.
• The enhanced dissolution is expected to improve drug absorption and therapeutic efficacy.
• The preparation method significantly influences the properties of the resulting inclusion complexes.