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Tropical Journal of Pharmaceutical Research

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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

Abstract


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



http://dx.doi.org/10.4314/tjpr.v17i12.1
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