Formulation of Dronedarone Hydrochloride-Loaded Proliposomes: In Vitro and In Vivo Evaluation Using Caco-2 and Rat...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology in Medicine

Background:

• Dronedarone hydrochloride (dronedarone HCl) exhibits poor oral bioavailability due to low solubility and absorption.
• Developing advanced drug delivery systems is crucial for improving the therapeutic efficacy of poorly soluble drugs.
• Proliposomes offer a promising approach to enhance the solubility and absorption of hydrophobic drugs.

Purpose of the Study:

• To develop and characterize a proliposomal formulation of dronedarone HCl.
• To enhance the solubility, dissolution, and intestinal absorption of dronedarone HCl.
• To evaluate the in vitro and in vivo performance of the optimized proliposomal formulation.

Main Methods:

• Proliposomes were prepared using the solvent evaporation method with various phospholipids (SPC, Phospholipon 90H, HEPC, DMPG) and cholesterol.
• Formulations underwent physical characterization and in vitro dissolution studies.
• In vitro intestinal permeability was assessed using Caco-2 cell monolayers.
• In vivo oral bioavailability was evaluated in male Sprague-Dawley rats.

Main Results:

• The optimized formulation (DPF8: drug:DMPG Na:cholesterol in 1:2:0.2 ratio) demonstrated superior drug release compared to pure dronedarone HCl.
• Caco-2 cell permeability studies showed a 2.6-fold increase in apparent permeability for the optimized formulation.
• In vivo studies in rats revealed a relative oral bioavailability of 148.36% for the optimized proliposomal formulation compared to the pure drug.

Conclusions:

• Optimized proliposomal formulation significantly enhances dronedarone HCl solubility and intestinal permeability.
• The developed proliposomes represent an effective strategy for improving the oral bioavailability of dronedarone HCl.
• This approach holds potential for enhancing the therapeutic outcomes of dronedarone HCl treatment.