Impact of uncharged and charged stabilizers on in vitro drug performances of clarithromycin nanocrystals

Abstract The purpose of this study was to evaluate the effect of charge on the in vitro drug performances of clarithromycin nanocrystals. To prepare different charges of nanocrystals, media milling was employed with the use of different stabilizing systems. The uncharged nanocrystals were prepared from poloxamer 407. The negatively and positively charged nanocrystals were stabilized using a combination of poloxamer 407 with sodium lauryl sulfate (SLS) and cetyltrimethylammonium bromide (CTAB), respectively. After production, the particle size of the negatively and positively charged nanocrystals was smaller than that of the uncharged one. The similar particle size of variously charged clarithromycin nanocrystals was selected to determine the in vitro drug performances. Dissolution profiles of the variously charged nanocrystals were similar; however, kinetic saturation solubility profiles were different. The positively charged nanocrystals showed higher mucoadhesiveness than the uncharged and the negatively charged nanocrystals. For drug permeation through NCI-N87 and Caco-2 cell monolayers, both charged nanocrystals showed a higher drug transport than the uncharged nanocrystals. It could be concluded that incorporating charge into clarithromycin nanocrystal formulations affected the particle size reduction process as well as the nanocrystal performances. Therefore, the surface charge is one of the crucial factors for the development of nanocrystal formulations.