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Jakab, Géza; Bogdán, Dóra; Mazák, Károly; Deme, Ruth; Mucsi, Zoltán; Mándity, István M.; Noszál, Béla; Kállai-Szabó, Nikolett; Antal, István

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

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  • Medientyp: E-Artikel
  • Titel: Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes
  • Beteiligte: Jakab, Géza; Bogdán, Dóra; Mazák, Károly; Deme, Ruth; Mucsi, Zoltán; Mándity, István M.; Noszál, Béla; Kállai-Szabó, Nikolett; Antal, István
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: AAPS PharmSciTech
  • Sprache: Englisch
  • DOI: 10.1208/s12249-019-1525-6
  • ISSN: 1530-9932
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>Baicalin is a flavone glycoside extracted from <jats:italic>Scutellaria baicalensis</jats:italic>, a traditional Chinese herbal medicine. Numerous pharmacological effects of baicalin were reported (<jats:italic>e.g.</jats:italic> 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 (log<jats:italic>P</jats:italic>) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility, <jats:sup>1</jats:sup>H/<jats:sup>13</jats:sup>C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (<jats:italic>P</jats:italic><jats:sub>app</jats:sub> = 0.037 × 10<jats:sup>−6</jats:sup> 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<jats:sup>−1</jats:sup> for β-CD, while it was significantly stronger for γ-CD (− 181.5 kJ mol<jats:sup>−1</jats:sup>). 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.</jats:p>