Effect of surfactants on the molecular mobility and crystallization kinetics of hesperetin

Abstract

Recent work from our lab studied the generation and performance evaluation of nanocrystalline solid dispersions (NCSDs) of a hesperetin-mannitol-sodium lauryl sulphate (SLS)-dioctyl sodium sulphosuccinate (DOSS) system. The NCSDs of hesperetin showed enhanced oral bioavailability compared to micronized hesperetin and offered anti-breast cancer activity in animal studies. The formulation can further be evaluated for treatment of inflammatory diseases and cancer. It was reported that hesperetin crystallization from its amorphous form is accelerated in the presence of mannitol. This work compares the effects of the incorporation of surfactants, SLS and DOSS on the crystallization kinetics of hesperetin along with mannitol. The molecular dynamics of amorphous hesperetin in the presence of excipients and their isothermal crystallization kinetics were studied using dielectric relaxation spectroscopy (DRS) and modulated differential scanning calorimetry (mDSC) techniques, respectively. Addition of a combination of SLS–DOSS yielded an approximately 11-fold decrease in α-relaxation times when compared with pure amorphous hesperetin. Secondly, the combination of SLS and DOSS promoted the nucleation of hesperetin while their crystal growth was hindered. This study illustrated the relationship between the crystallite size of hesperetin NCSDs and the type of excipient/surface modifier(s).