Study on Acute Toxicity of Amiodarone New Complexes With Cyclodextrin

Area of Science:

• Pharmacology
• Drug Delivery
• Toxicology

Background:

• Amiodarone's low solubility limits bioavailability and increases toxicity.
• Cyclodextrin complexation improves amiodarone dissolution, solubility, and drug release control.

Purpose of the Study:

• To characterize the acute toxicity of a novel amiodarone 2-hydroxypropyl-β-cyclodextrin complex (AMD/HP-β-CD).
• To evaluate two matrix formulations (Kollidon® and chitosan-based) for amiodarone delivery.

Main Methods:

• Intraperitoneal administration of amiodarone, AMD/HP-β-CD, and matrix formulations in laboratory animals.
• Acute toxicity assessment, including determination of LD50 values and histopathological analysis.

Main Results:

• Amiodarone and AMD/HP-β-CD showed equitoxicity (LD50 ≈ 289-298 mg/kg) with similar histopathological changes.
• Matrix formulations (Fc and F10) exhibited higher LD50 values (347.5 mg/kg and 455.6 mg/kg, respectively).
• The Kollidon® and chitosan matrix significantly increased the LD50 of the amiodarone complex by 1.5 times compared to pure amiodarone.

Conclusions:

• Kollidon® and chitosan matrices modify amiodarone solubility and control its release, enhancing safety.
• The developed matrix formulations offer a safer route for amiodarone administration.
• AMD/HP-β-CD complexation within a KOL and CHT matrix presents a promising approach to mitigate amiodarone toxicity.