Permeability Enhancing Lipid-Based Co-Solvent and SEDDS Formulations of SQ641, an Antimycobacterial Agent

SRI Authors: Shravan K Mutyam, Gita Shankar

Abstract

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.