Posted by The Bubble-Driven Drug Delivery System (BDDS, a new name for effervescent formulations) was optimized through the screening of effervescent formulations (citric acid: Na2CO3 = 6:5) and bile salts (sodium deoxycholate, SDC) (1). Its performance was comprehensively assessed via in vitro dissolution tests, an everted intestinal sac assay, Caco-2 cell monolayer experiments, pharmacokinetic studies, and yeast-induced fever rat models.
The BDDS achieved 75.0%– 88.7% dissolution in gastrointestinal pH media, which was markedly superior to that of commercial dripping pills (DP; 30.5– 50.2%). Its apparent permeability coefficient was 7.7-fold and 3.6-fold higher than that of free Andrographolide (AG) and DP, respectively. Transport studies indicated that SDC enhanced AG permeability primarily via the apical sodium-dependent bile acid transporter (ASBT)-mediated pathway, a mechanism further confirmed by inhibition with linerixibat. The relative oral bioavailability of BDDS versus DP reached 257.1%. BDDS demonstrated enhanced efficacy by significantly inhibiting key pro-inflammatory cytokines and thermoregulatory mediators in yeast-induced fever rats.
The BDDS effectively overcomes AG’s low solubility (by SDC solubilization and CO2 bubbles) and permeability (via ASBT transport), outperforming conventional formulations in terms of preparation simplicity and storage stability.
A recent review summarizes progress in andrographolide’s anti-infective applications, focusing on its structure–activity relationship (SAR) and mechanisms of action (2). Researchers have used semi-synthetic methods, such as esterification, oxidation, Michael addition, salification, and hybrid design, to enhance andrographolide’s physicochemical properties and biological activity. These derivatives show potent antiviral activity against RNA and DNA viruses, antibacterial activity against Gram-positive and Gram-negative bacteria, antifungal effects, and antiparasitic activity against Plasmodium spp. and Leishmania spp. Nevertheless, poor solubility and limited bioavailability still hinder their clinical translation. Strategies such as nano delivery systems and β-cyclodextrin complexes are discussed to improve bioavailability. Although andrographolide itself has not received regulatory approval as a stand-alone drug, several andrographolide-containing preparations have been clinically used in certain countries.
The solubility isotherm is of Bs type showing precipitation of the β-cyclodextrin complex at higher CD concentrations (3), while it is of AL type with HPBCD (4). The stoichiometry of the complex is 1:1. The peak concentration of the drug in the presence of β-cyclodextrin is double of that in its absence, while HPBCD enhanced the solubility to more than tenfold.
The chemical structure of andrographolide
References:
(1) Zhou J, Luo W, Zeng L, Xu S, Wu R, Lu J, Li Y, Xiong W. (2026) A Bubble-Driven Drug Delivery System Enhances Oral Absorption and Antipyretic Efficacy of Poorly Water-Soluble Andrographolide. Int J Nanomedicine. 2026;21:574265. https://doi.org/10.2147/IJN.S574265
(2) Ren, Z., Chen, Z., Xie, Y., & Coghi, P. (2025). Andrographolide and Its Derivatives: A Comprehensive Review of Anti-Infective Properties and Clinical Potential. Molecules, 30(21), 4273. https://doi.org/10.3390/molecules30214273
(3) Zhao, D., Liao, K., Ma, X. et al. Study of the Supramolecular Inclusion of β-Cyclodextrin with Andrographolide. Journal of Inclusion Phenomena 43, 259–264 (2002). https://doi.org/10.1023/A:1021223407297