(Open access funding provided by Semmelweis University)
Baicalin is a flavone glycoside extracted from Scutellaria baicalensis,
a traditional Chinese herbal medicine. Numerous pharmacological effects of baicalin
were reported (e.g. antioxidant, anxiolytic); nevertheless,
the most important physicochemical properties influencing the pharmacokinetic behaviour
and the concomitant oral bioavailability have not yet been described in a comprehensive
study. The aim of this project was to characterize the acid-base, lipophilicity, biorelevant
solubility and permeability properties of the drug substance and providing scientific
data to support the dosage form design. Another important objective was the comparative
evaluation of six various baicalin-cyclodextrin (CD) inclusion complexes along with
the creation of a suitable Drug Delivery System (DDS) for this BCS IV drug. Biorelevant
profiling was carried out by NMR-pH titrations, saturation shake-flask and distribution
coefficients (logP) measurements, while CD inclusion studies
were fulfilled by experimental methods (phase solubility, 1H/13C
NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03
± 1.60 μg/ml) and low permeability (Papp
= 0.037 × 10−6 cm/s), baicalin is classified as BCS IV. The γ-CD
complexation significantly increased the solubility of baicalin (~ 5 times). The most
promoted chemical shift change occurred in baicalin-γ-CD complex. Computational studies
showed disparate binding pattern for baicalin in case of β- and γ-CD; furthermore,
the calculated complexation energy was − 162.4 kJ mol−1 for β-CD,
while it was significantly stronger for γ-CD (− 181.5 kJ mol−1).
The physicochemical and structural information of baicalin and its CD complexes introduced
herein can create molecular basis for a promising DDS with enhanced bioavailability
containing a bioactive phytopharmacon.
