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Biomedical sciences publications June 1, 2014

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

SRI Authors: Shravan K Mutyam, Gita Shankar

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Mutyam, S. K., Bejugam, N. K., Parish, H. J., Reddy, V. M., Bogatcheva, E., & Shankar, G. N. (2014). Permeability enhancing lipid-based co-solvent and SEDDS formulations of SQ641, an antimycobacterial agent. Pharmaceutical Development and Technology, 1-10. doi: 10.3109/10837450.2014.908304

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.

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