Abstract

Background and Objective: Glycyrrhetinic acid (GHA) potential has therapeutic and nutricosmetic activity. Poor aqueous solubility is the main limiting factor in usage of GHA in variety of application. The main objective of this study is to improve aqueous solubility of GHA by using various nanonization techniques.

Method: GHA nanocrystals were prepared by three different top down technologies. GHA (5% w/w) was dispersed in aqueous surfactant solution [1% (w/w) Plantacare 2000 UP or Tween 80] to prepare the coarse suspension. Nanocrystals were produced by using techniques like high pressure homogenization (HPH), bead milling (BM) and combination technology (CT, BM followed by HPH). Nanocrystals were characterized for their particle size, zeta potential (ZP), agglomeration behavior and crystallinity by powder X-ray diffraction (PXRD) pattern. The long term stability of the GHA nanocrystals were assessed in three different storage conditions i.e. 4°C, 25°C and 40°C.

Results: The CT process produced smallest size nanocrystal (smartCrystal^®), i.e. 155 nm, compared to HPH (324 nm) and BM (268 nm). Plantacare 2000 UP had a better stabilization effect compared to Tween 80. Saturation solubility study showed particle size dependent increase in solubility. Smallest nanocrystal obtained by CT process had highest solubility followed by nanocrystals obtained by BM and HPH process.

Conclusion: The selection of suitable stabilizer with optimal performance and production method are crucial for producing nanocrystals having good stability profile. Among the production methods used, CT process produced stable narrow particle size range crystals with enhanced solubility profile.

Keywords: Glycyrrhetinic acid, glycyrrhizic acid, nanocrystals, production methods, high pressure homogenization, bead milling, combination technology, smartCrystal^®

Graphical Abstract