Jakab Géza, Antal István
Semmelweis University, Department of Pharmaceutics, Budapest
Introduction: Baicalin is a flavone glycoside extracted from the root of Scutellaria baicalensis, a traditional Chinese herbal medicine. The root is officially listed in the Chinese Pharmacopoeia and was assumed in European Pharmacopoeia (Ph.Eur.) 9th Edition last year. 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.
Aims: This research has therefore aimed to characterize the acid-base, lipophilicity, biorelevant solubility and permeability properties of this naturally occurring compound. Another important goal was the comparative evaluation of six different baicalin-cyclodextrin (CD) inclusion complexes.
Method: The physicochemical quantification was fulfilled using NMR-pH titrations, saturation shake-flask, and distribution coefficients measurements. CD complexation of baicalin was examined by experimental methods (phase solubility, 1H NMR, 2D ROESY) and computational approaches.
Results: 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. Significant solubilizing impact of biorelevant fasted state gastric juice (33.21 ± 0.72 µg/ml) was found to be correlated to compendial pH 1.2 gastric fluid (11.64 ± 0.44 µg/ml). The γ-CD complexation significantly increased the solubility of baicalin (~5 times). The most promoted chemical shift change was detected in baicalin-γ-CD complex. Computational studies showed disparate binding pattern for β-, and γ-CD, which can be explained in terms of the diameter, related to the respective 7 and 8 glucose units in β and γ-CDs.
Conclusions: The physicochemical and structural information of baicalin and its CD complexes introduced herein can create molecular basis for a promising Drug Delivery System with enhanced bioavailability containing a bioactive phytopharmacon.
Doctoral School: Pharmaceutical Sciences
Program: Modern Trends in Pharmaceutical Scientific Research
Supervisor: Antal István
E-mail address: email@example.com