Tropical Journal of Pharmaceutical Research

Log in or Register to get access to full text downloads.

Remember me or Register

Preparation, characterization, intrinsic dissolution studies and microbiological assessment of dapsone tosylate polymorphs

Daniela Flores-Pacheco, Karina Mondragón-Vásquez, Jorge G. Domínguez-Chávez, Blanca E. Duque-Montaño, Oscar Torres-Ángeles, Jesús Rivera-Islas


Purpose: To prepare dapsone tosylate salt (TD) and its two polymorphs (TD-I and TD-II), and study their intrinsic dissolution profiles and preliminary anti-mycobacterium activity.

Methods: The synthesized product was studied with respect to the effect of solvent selection, reaction temperature and evaporation rate on the solid phase obtained. The polymorphs were characterized using powder x-ray diffraction (PXRD), proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). UV/Vis spectroscopy was employed for quantification of the salt, while Wood apparatus was used for dissolution studies. Microdilution assay, using a 96-well equipment, was employed for the evaluation of anti-mycobacterial activity.

Results: On analysis of the solids obtained from synthesis with PXRD, two different patterns were observed. One pattern belonged to TD-I, previously reported, and the other was a new polymorph TD-II. Solvent evaporation was important in the selective preparation of TD-I or TD-II. Analyses with DSC, TGA and 1H-NMR revealed the absence of solvent in both solids and showed that TD-II was not a solvated salt. Spectral analysis with FT-IR demonstrated structural relationship between TD-I and TD-II. Intrinsic dissolution studies showed that both polymorphs dissolved faster than dapsone (DAP).

Conclusion: It is possible to synthesize TD and select the polymorph prepared by means of modulated solvent evaporation rate. The rank order of the intrinsic dissolution rate constants was TD-II > TD-I > DAP. The tosylate salt enhanced inhibitory effect on M. fortuitum, when compared to DAP.

Keywords: Dapsone tosylate, Polymorphism, Solid phase characteristics, Intrinsic dissolution, Antimycobacterium activity
AJOL African Journals Online