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
| Autor: | Matteo Lusi, Conor Madden, Sarah P. Hudson, Edel Durack, Pauric Bannigan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Drug
medicine.drug_class General Chemical Engineering media_common.quotation_subject 02 engineering and technology Pharmacology Antimycobacterial 01 natural sciences Article Clofazimine lcsh:Chemistry medicine Solubility Dissolution media_common 010405 organic chemistry Chemistry General Chemistry 021001 nanoscience & nanotechnology medicine.disease Antimicrobial In vitro 3. Good health 0104 chemical sciences lcsh:QD1-999 Leprosy 0210 nano-technology medicine.drug |
| Zdroj: | ACS Omega ACS Omega, Vol 2, Iss 12, Pp 8969-8981 (2017) |
| ISSN: | 2470-1343 |
| Popis: | 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. Salts forms which showed superior stability as well as solubility and activity to the commercial drug formulation were fully characterized using a combination of spectroscopic techniques, including X-ray diffraction, solid-state NMR, and Fourier transform infrared spectroscopy. |
| Databáze: | OpenAIRE |
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