Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes

Géza Jakab, Dóra Bogdán, Károly Mazák, Ruth Deme, Zoltán Mucsi, I. Mándity, B. Noszál, Nikolett Kállai-Szabó, I. Antal

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Number of pages1
JournalAAPS PharmSciTech
Volume20
Issue number8
DOIs
Publication statusPublished - Sep 16 2019

Keywords

  • baicalin
  • computational modelling
  • cyclodextrins
  • physicochemical analysis
  • solubility enhancement

ASJC Scopus subject areas

  • Pharmaceutical Science

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