β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Diminazene aceturate (DA) exhibits poor bioavailability due to rapid degradation in acidic stomach conditions.
• Improving DA's therapeutic index requires formulations that enhance its stability and absorption.
• Beta-cyclodextrin (βCD) is a potential host molecule for stabilizing pharmaceutical compounds.

Purpose of the Study:

• To develop and characterize a diminazene aceturate:β-cyclodextrin (DA:βCD) inclusion complex.
• To enhance the bioavailability and stability of DA by protecting it from gastric degradation.
• To evaluate the in vitro and in vivo biological activity of the DA:βCD inclusion complex.

Main Methods:

• Complexation of DA within βCD cavity at a 1:1 molar ratio.
• Structural characterization using Raman, DSC, WAXD, 1H-NMR, and H-H ROESY.
• Stoichiometry determination via Job's plot and 1H-NMR.
• In vitro antioxidant activity assays.
• In vivo bioavailability studies in Wistar rats using HPLC analysis of blood plasma.

Main Results:

• The DA:βCD inclusion complex was successfully formed and characterized in solid and solution states.
• In vitro studies demonstrated improved antioxidant activity for the complex.
• In vivo studies showed significantly higher DA concentrations in rat blood plasma (up to 11-fold at 60 min) when administered as the 1:1 DA:βCD inclusion complex compared to free DA.

Conclusions:

• The 1:1 molar ratio DA:βCD inclusion complex effectively protects DA from degradation and enhances its oral bioavailability.
• This formulation strategy offers a promising approach to improve the therapeutic efficacy of diminazene aceturate in animal treatments.
• The enhanced stability and absorption profile suggest potential for increased therapeutic index and reduced dosing frequency.