A Natural Triterpenoid Saponin as Multifunctional Stabilizer for Drug Nanosuspension Powder

AAPS PharmSciTech. 2017 Oct;18(7):2744-2753. doi: 10.1208/s12249-017-0756-7. Epub 2017 Mar 24.

Abstract

The objective of this study is to prepare a novel drug nanosuspension modified by a natural triterpenoid saponin (glycyrrhizin (GZ)) and evaluate its stability and redispersibility. A poorly soluble drug (andrographolide (AGE)) was used as a model drug. AGE nanosuspensions (AGE-NS) using GZ as natural stabilizer with mean particle size of 487 nm were firstly prepared by homogenization and converted into dried AGE nanosuspension powder (AGE-NP) by freeze-drying. It was found that GZ was able to prevent the aggregation of AGE nanocrystals and the freeze-dried AGE-NP could easily redisperse back to AGE-NS. It was related with special properties of GZ that possessed the interfacial property (37.02 ± 0.29 N/m) and electrostatic effect (-43.6 ± 0.9 mV) and could entrap AGE nanocrystals into its network structure. The freeze-dried AGE-NP/GZ exhibited excellent performance, compared with those combined with trehalose as matrix formers. The powder X-ray diffraction result demonstrated that GZ did not alter the AGE crystal state. The dissolution of AGE-NP/GZ (99.87%) was significantly enhanced, compared with the coarse AGE (42.35%). This study demonstrated that GZ could be used as a novel multifunctional stabilizer for production of drug nanosuspensions and provided a promising basis for further formulation development of poorly soluble drug.

Keywords: freeze-drying; glycyrrhizin; nanosuspensions; redispersibility; stabilizer.

MeSH terms

  • Diterpenes / chemistry*
  • Drug Stability
  • Freeze Drying
  • Glycyrrhizic Acid / chemistry*
  • Nanoparticles / chemistry
  • Powders
  • Solubility
  • Suspensions

Substances

  • Diterpenes
  • Powders
  • Suspensions
  • andrographolide
  • Glycyrrhizic Acid