Unraveling\nthe Impact of Stabilizers on Nanocrystal\nPreparation and Oral Absorption: A Case Study of Poorly Soluble Andrographolide

Drug nanocrystal engineering is an attractive pharmaceutical\napproach\nto enhancing the oral bioavailability of poorly soluble drugs. The\nmechanism of drug nanocrystal stabilization, however, is unclear.\nHere we developed andrographolide nanocrystals (AG-NCs) with various\nnonionic surfactants (Pluronic-F127, TPGS, or Brij-S20). We detected\nAG micelles (AG-MCs) at an andrographolide to nonionic surfactant\nratio of 10:10 (w/w) and poor AG-NC size stability. We thus quantified\nthe unbound Pluronic-F127 in AG-NCs and found that the proposed instantaneous\nbinding rate sharply declined with increasing Pluronic-F127 input.\nWe determined that the saturation dose of TPGS on AG-NCs was approximately\n10:10 (w/w) and recommend it as a key criterion for nanocrystal formulation.\nAlthough AG-NCs exhibited a marginally faster dissolution rate, they\npossessed better mucus-penetrating and transmembrane transport capacities\nand significantly enhanced oral absorption compared to AG-MCs. These\nfindings give insights into the impact of a stabilizer during the\npreparation process and the oral absorption of drug nanocrystals.