Permeability enhancing lipid-based co-solvent and SEDDS formulations of SQ641, an antimycobacterial agent

Abstract

Context: Tuberculosis (TB) is a common and often deadly infectious disease caused by strains of Mycobacteria. Development of new anti-tubercular drugs is essential to control the emergence and severity of multidrug-resistant TB.

Objective: The objective of this study was to develop an oral preclinical liquid formulation of SQ641 and to determine the permeability across rat intestinal tissue by Ussing chamber.

Methods: Thermal and chemical characterization of SQ641 was performed by differential scanning calorimetric analysis, thermogravimetric analysis and high performance liquid chromatography. A high throughput solubility screening technique was utilized to determine the solubility of SQ641 in different solvents and co-solvents. Several co-solvent and self-emulsifying drug delivery system (SEDDS) formulations were selected for Ussing chamber permeability studies.

Results and discussion: Calculated average apparent permeability coefficients of SEDDS formulations of SQ641 (ranging from 0.03 × 10⁻⁶ to 0.33 × 10⁻⁶) were found to be higher than the permeability coefficients of co-solvent formulations (ranging from 0.00 × 10⁻⁶ to 0.09 × 10⁻⁶) and those of the neat drug SQ641 in buffer (0.00 × 10⁻⁶).

Conclusion: SEDDS formulations with superior permeability characteristics may provide a useful dosage form for oral intake of anti-tubercular drug SQ641, possibly due to the increase in solubility and immediate dispersion of drug.

• Emulsion
• HTS
• permeability
• solubility
• tuberculosis
• Ussing chamber

Acknowledgements

The authors wish to thank Elaine Struble for HPLC analysis and Paul Penwell for DSC and TGA analysis.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. This project has been funded in whole or in part with federal funds from the US National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the US Department of Health and Human Services under Contract No. HHSN266200600011C/N01-AI-60011.