Third Generation Solid Dispersion-Based Formulation of Novel Anti-Tubercular Agent Exhibited Improvement in...

Area of Science:

• Pharmaceutical Sciences
• Medicinal Chemistry
• Drug Delivery

Background:

• Tuberculosis (TB) treatment faces challenges due to long durations and emerging drug resistance.
• New anti-tubercular agents are essential, leading to the development of IIIM-019, a promising nitrodihydroimidazooxazole analogue.
• IIIM-019 exhibits poor aqueous solubility (1.2 µg/mL), hindering efficient oral administration and necessitating advanced formulation strategies.

Purpose of the Study:

• To develop a third-generation solid dispersion formulation to enhance the solubility and dissolution of the anti-tubercular lead IIIM-019.
• To improve the oral bioavailability and therapeutic efficacy of IIIM-019 through advanced drug delivery.
• To evaluate the physicochemical properties, safety, and anti-tubercular activity of the developed solid dispersion formulation.

Main Methods:

• Solubility studies were conducted using various polymeric carriers, with PVP K-30 and P-407 selected for binary and ternary solid dispersions.
• Physicochemical characterization involved FTIR, SEM, XRD, DSC, and DLS analyses.
• In vitro evaluations included cytotoxicity assays on Caco-2 cells, hemolytic activity tests, and anti-tubercular activity assessments.

Main Results:

• The ternary solid dispersion formulation containing PVP K-30 and P-407 significantly enhanced the aqueous solubility and dissolution of IIIM-019.
• Characterization confirmed the successful formation of the solid dispersion with improved physicochemical properties.
• The optimized formulation demonstrated no significant cytotoxicity or hemolytic activity and exhibited markedly improved anti-tubercular efficacy compared to the native IIIM-019.

Conclusions:

• The developed third-generation ternary solid dispersion represents a promising approach for enhancing the oral delivery of the anti-tubercular molecule IIIM-019.
• This formulation strategy effectively overcomes the poor aqueous solubility limitations of IIIM-019.
• The enhanced solubility and improved anti-tubercular activity suggest significant therapeutic potential for this novel drug delivery system in combating tuberculosis.