Improved Pharmaceutical Properties of Honokiol via Salification with Meglumine: an Exception to Oft-quoted ∆pKa Rule

Honokiol (HK), a BCS class II drug with a wide range of pharmacological activities, has poor solubility and low oral bioavailability, severely limiting its clinical application. In the current study, incorporating a water-soluble meglumine (MEG) into the crystal lattice of HK molecule was performed...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutical research 2022-09, Vol.39 (9), p.2263-2276
Main Authors: He, Xiaoshuang, Wei, Yuanfeng, Wang, Shiru, Zhang, Jianjun, Gao, Yuan, Qian, Shuai, Pang, Zunting, Heng, Weili
Format: Article
Language:English
Subjects:
Bioavailability
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Hydrogen bonding
Medical Law
Original Research Article
Pharmacokinetics
Pharmacology/Toxicology
Pharmacy
Physicochemical properties
Solubility
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Honokiol (HK), a BCS class II drug with a wide range of pharmacological activities, has poor solubility and low oral bioavailability, severely limiting its clinical application. In the current study, incorporating a water-soluble meglumine (MEG) into the crystal lattice of HK molecule was performed to improve its physicochemical properties. The binary mixture of HK and MEG was obtained by anti-solvent method and characterized by TGA, DSC, FTIR, and PXRD. The SCXRD analysis showed that two HK − molecules and two MEG + molecules were coupled in each unit cell via the ionic interaction along with intermolecular hydrogen bonds, suggesting the formation of a salt, which was further confirmed by the XPS measurements. However, the ∆pK a value between HK and MEG was found to be less than 1, which did not follow the oft-quoted ∆pK a rule for salt formation. After salification with MEG, the solubility and dissolution rate of HK exhibited 3.50 and 25.33 times improvement than crystalline HK, respectively. Simultaneously, the powder flowability, tabletability and stability of HK-MEG salt was also significantly enhanced, and the salt was not more hygroscopic, and that salt formation did not compromise processability in that regard. Further, in vivo pharmacokinetic study showed that C max and AUC 0-t of HK-MEG salt were enhanced by 2.92-fold and 2.01-fold compared to those of HK, respectively, indicating a considerable improvement in HK oral bioavailability.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-022-03335-6