Pharmaceutical salt of BM635 with improved bioavailability

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Drug Discovery

Background:

• BM635 exhibits potent anti-mycobacterial activity against Mycobacterium tuberculosis.
• Poor aqueous solubility and high lipophilicity limit BM635's in vivo exposure and bioavailability.
• The drug has a short in vivo half-life (1 hour) and moderate Cmax (1.62μM) and bioavailability (46%).

Purpose of the Study:

• To develop pharmaceutically acceptable salt forms of BM635.
• To overcome the solubility and bioavailability limitations of the parent compound.
• To evaluate the physicochemical and biopharmaceutical properties of novel BM635 salts.

Main Methods:

• Salt formation of BM635 with hydrochloric, methanesulphonic, phosphoric, tartaric, and citric acids.
• Evaluation of physicochemical properties of BM635 salts.
• Assessment of biopharmaceutical attributes of BM635 salts.

Main Results:

• Development of five BM635 salt forms: BM635-HCl, BM635-Mes, BM635-PA, BM635-TA, and BM635-CA.
• Initial evaluation of physicochemical and biopharmaceutical properties of these salts.
• Identification of potential improvements over the parent BM635 compound.

Conclusions:

• Salt formation is a viable strategy to enhance the drug-like properties of BM635.
• The developed salt forms hold promise for improving the therapeutic potential of BM635 in tuberculosis treatment.
• Further studies are warranted to fully characterize and optimize these novel formulations.