Pre-Formulation Studies of Lipid-Based Formulation Approach for a Poorly Water-Soluble Biopharmaceutics...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Bosentan monohydrate (BOS) exhibits poor solubility, limiting its therapeutic efficacy.
• Lipid-based formulations, such as self-nanoemulsifying drug delivery systems (SNEDDS), offer a promising approach to enhance the solubility of poorly soluble drugs.

Purpose of the Study:

• To develop and optimize self-nanoemulsifying drug delivery systems (SNEDDS) for bosentan monohydrate (BOS).
• To evaluate the pre-formulation, formulation, and characterization of BOS-loaded SNEDDS.
• To assess the in vitro dissolution and ex vivo permeability of the optimized formulation.

Main Methods:

• Pseudo-ternary phase diagrams were utilized for SNEDDS formulation design.
• Response surface methodology (Box-Behnken Design) was employed for formulation optimization.
• Characterization included droplet size, PDI, dispersibility, self-emulsification efficiency, stability studies, in vitro dissolution, and ex vivo permeation.

Main Results:

• The optimized BOS-loaded SNEDDS exhibited a small droplet size (16.76 nm) and narrow PDI (0.200).
• The formulation demonstrated excellent self-emulsification properties, stability across different pH and temperatures, and was stable for six months.
• Significant increases in in vitro dissolution (up to 4.23-fold) and ex vivo drug permeation (up to 20.3-fold) were observed compared to the commercial product.

Conclusions:

• Optimized BOS-loaded SNEDDS were successfully developed, demonstrating enhanced solubility, dissolution, and permeability.
• The lipid-based SNEDDS formulation shows great potential for improving the oral bioavailability of bosentan monohydrate.
• This formulation approach warrants further investigation in in vivo studies.