Role of Biorelevant Dissolution Media in the Selection of Optimal Salt Forms of Oral Drugs: Maximizing the Gastrointestinal Solubility and in Vitro Activity of the Antimicrobial Molecule, Clofazimine

ACS Omega
Pauric BanniganSarah P Hudson

Abstract

Clofazimine is an antimycobacterial agent that is routinely used for the treatment of leprosy. Clofazimine has also been shown to have high clinical potential for the treatment of many Gram-positive pathogens, including those that exhibit high levels of antibiotic resistance in the medical community. The use of clofazimine against these pathogens has largely been limited by the inherently poor water solubility of the drug substance. In this work, the possibility of repurposing and reformulating clofazimine to maximize its clinical potential is investigated. To achieve this, the potential of novel salt forms of clofazimine as supersaturating drug-delivery vehicles to enhance the aqueous solubility and gastrointestinal solubility of the drug substance was explored. The solution properties of seven novel salt forms, identified during an initial screening process, were examined in water and in a gastrointestinal-like media and were compared and contrasted with those of the free base, clofazimine, and the commercial formulation of the drug, Lamprene. The stability of the most promising solid forms was tested, and their bioactivity against Staphylococcus aureus was also compared with that of the clofazimine free base and Lamprene. Sa...Continue Reading

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Citations

Aug 25, 2020·Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials·Laurie BodartJohan Wouters
Apr 13, 2020·Journal of Colloid and Interface Science·Michele DullySarah P Hudson
Apr 21, 2021·Drug Delivery and Translational Research·Aoibhín RyanSarah P Hudson

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Methods Mentioned

BETA
X-ray
nuclear
NMR
nuclear magnetic resonance
saturation recovery

Software Mentioned

FaSSIF
SSNMR
Cambridge Structural Databank ( CSD )
FaSSGF
SHELX
Mercury
SEED

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