Objective: The study aimed to evaluate the critical physicochemical properties (lipophilicity, aqueous solubility, and degree of ionization) of atractylodin and β-eudesmol using in vitro testing.
Methods: Lipophilicity (Log P and Log D) was determined using the shake-flask method (n-octanol/water partition). Aqueous solubility was determined using kinetic solubility assay in media with pH ranging from 1.2 to 7.4. The degree of ionization (pKa) was determined using the potentiometric titration method.
Results: Log P and Log D values of 3.0-5.0 suggested moderate lipophilicity of both compounds. Both exhibited low aqueous solubility over the investigated pH range (0.08-0.93 and 1.97-32.48 μg/ml for atractylodin and β-eudesmol, respectively). Based on the pKa values of 9.63 (atractylodin) and 9.12 (b-eudesmol), both are classified as basidic compounds.
Conclusion: Atractylodin and β-eudesmol are classified as BCS class II drugs. The physicochemical parameters of both compounds obtained from the current study will be further applied for in silico prediction of their ADME (absorption, distribution, metabolism, and excretion) properties. In addition, PBPK modeling will be used for the prediction of optimal dose regimens of the capsule formulation of the standardized extract of Atractylodes lancea for first-in-human (FIH) and phase II studies in patients with cholangiocarcinoma
