Application of ascorbic acid 2-glucoside as a solubilizing agent for clarithromycin: Solubilization and nanoparticle formation

Abstract

Clarithromycin (CAM) was co-ground with l-ascorbic acid 2-glucoside (AA-2G), a newly developed food additive, to improve the solubility characteristics. The complete solubilizing effect of AA-2G was observed for the ground mixture with 1:1 molar ratio. When ground mixtures of CAM and AA-2G (2:1) were dispersed into water, not only the solubilization of CAM was observed but also nanoparticle formation with a mean particle diameter of 280 nm. The CAM particles obtained in this manner were stable in suspension for at least 7 days. Zeta potential analysis showed that positive charges on the particle surface may be contributing to the stability of the suspension. 1H NMR spectrum of CAM dissolved in a phosphate buffer (pH 5.5) showed a signal derived from the N, N-dimethylamino group at 2.73 ppm, while that of an equimolar ground mixture of CAM with AA-2G in D 2O (pH 5.5) showed clearly two signals at 2.65 and 2.77 ppm derived from the splitting of the two methyl groups. The 13C NMR spectrum of the equimolar ground mixture dissolved in D 2O exhibited two signals derived from N, N-dimethyl carbons of desosamine group at 37.2 and 42.3 ppm, whereas unprocessed CAM showed no resonance signal arising from those carbons. Moreover, the carbon resonance at 163 and 173 ppm arising from the ketone group in the CAM lactone ring shifted downfield to 177 and 180 ppm after the co-grinding with AA-2G. The formation of nanoparticles was only observed when CAM was co-ground with AA-2G in the molar ratio of 2:1, which might be attributable to a grinding-induced interaction in the solid-state via the ketone group in lactone ring of CAM.