Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes
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 beha...
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| Veröffentlicht in: | AAPS PharmSciTech 2019-09, Vol.20 (8), p.314-314, Article 314 |
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| creator | Jakab, Géza Bogdán, Dóra Mazák, Károly Deme, Ruth Mucsi, Zoltán Mándity, István M. Noszál, Béla Kállai-Szabó, Nikolett Antal, István |
| description | 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 (log
P
) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility,
1
H/
13
C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (
P
app
= 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. |
| doi_str_mv | 10.1208/s12249-019-1525-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6746686</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2293005411</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-9330ab3bc1180afc19bb6eb78275ba9a7d3ee82e1f7fa3b86d0e757c75361b2b3</originalsourceid><addsrcrecordid>eNp9kUtP3TAUhK2KCijtD-gGZckmrR9JHG-QIH0hIZVFu7Zs5-TGyLEvdgLc_vo6uoDopitbZ74ZH3kQ-kjwJ0Jx-zkRSitRYiJKUtO6bN6gY1IzXArB6MGr-xF6l9ItxpQRwQ7REcu4ILw-RrubcZesCWaEyRrlipsYBuus3xRhKC7VOrO-uHAhTx7sPBbzCMUXuAcXthP4uVC-L7pRRWVmiPaPmm3wq7fbGRd6eJxj9l9545a0Kl2Ytg4eIb1HbwflEnx4Ok_Q729ff3U_yuuf36-6i-vSVBWdS8EYVpppQ0iL1WCI0LoBzVvKa62E4j0DaCmQgQ-K6bbpMfCaG16zhmiq2Qk63-duFz1Bb_LOUTm5jXZScSeDsvJfxdtRbsK9bHjVNG2TA86eAmK4WyDNcrLJgHPKQ1iSpFQwjOuKkIySPWpiSCnC8PIMwXKtTO4rk7kyuVYm1_jT1_u9OJ47ygDdAylLfgNR3oYl-vxn_0n9C_bLpZs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2293005411</pqid></control><display><type>article</type><title>Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Jakab, Géza ; Bogdán, Dóra ; Mazák, Károly ; Deme, Ruth ; Mucsi, Zoltán ; Mándity, István M. ; Noszál, Béla ; Kállai-Szabó, Nikolett ; Antal, István</creator><creatorcontrib>Jakab, Géza ; Bogdán, Dóra ; Mazák, Károly ; Deme, Ruth ; Mucsi, Zoltán ; Mándity, István M. ; Noszál, Béla ; Kállai-Szabó, Nikolett ; Antal, István</creatorcontrib><description>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 (log
P
) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility,
1
H/
13
C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (
P
app
= 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.</description><identifier>ISSN: 1530-9932</identifier><identifier>EISSN: 1530-9932</identifier><identifier>DOI: 10.1208/s12249-019-1525-6</identifier><identifier>PMID: 31529175</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Antineoplastic Agents, Phytogenic - administration & dosage ; Antineoplastic Agents, Phytogenic - chemistry ; Biochemistry ; Biological Availability ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cyclodextrins - chemistry ; Drug Delivery Systems ; Flavonoids - administration & dosage ; Flavonoids - chemistry ; Lipids - chemistry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Permeability ; Pharmacology/Toxicology ; Pharmacy ; Research Article ; Solubility ; Thermodynamics</subject><ispartof>AAPS PharmSciTech, 2019-09, Vol.20 (8), p.314-314, Article 314</ispartof><rights>The Author(s) 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-9330ab3bc1180afc19bb6eb78275ba9a7d3ee82e1f7fa3b86d0e757c75361b2b3</citedby><cites>FETCH-LOGICAL-c442t-9330ab3bc1180afc19bb6eb78275ba9a7d3ee82e1f7fa3b86d0e757c75361b2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1208/s12249-019-1525-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1208/s12249-019-1525-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31529175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jakab, Géza</creatorcontrib><creatorcontrib>Bogdán, Dóra</creatorcontrib><creatorcontrib>Mazák, Károly</creatorcontrib><creatorcontrib>Deme, Ruth</creatorcontrib><creatorcontrib>Mucsi, Zoltán</creatorcontrib><creatorcontrib>Mándity, István M.</creatorcontrib><creatorcontrib>Noszál, Béla</creatorcontrib><creatorcontrib>Kállai-Szabó, Nikolett</creatorcontrib><creatorcontrib>Antal, István</creatorcontrib><title>Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes</title><title>AAPS PharmSciTech</title><addtitle>AAPS PharmSciTech</addtitle><addtitle>AAPS PharmSciTech</addtitle><description>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 (log
P
) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility,
1
H/
13
C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (
P
app
= 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.</description><subject>Antineoplastic Agents, Phytogenic - administration & dosage</subject><subject>Antineoplastic Agents, Phytogenic - chemistry</subject><subject>Biochemistry</subject><subject>Biological Availability</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cyclodextrins - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Flavonoids - administration & dosage</subject><subject>Flavonoids - chemistry</subject><subject>Lipids - chemistry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Models, Molecular</subject><subject>Permeability</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Research Article</subject><subject>Solubility</subject><subject>Thermodynamics</subject><issn>1530-9932</issn><issn>1530-9932</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtP3TAUhK2KCijtD-gGZckmrR9JHG-QIH0hIZVFu7Zs5-TGyLEvdgLc_vo6uoDopitbZ74ZH3kQ-kjwJ0Jx-zkRSitRYiJKUtO6bN6gY1IzXArB6MGr-xF6l9ItxpQRwQ7REcu4ILw-RrubcZesCWaEyRrlipsYBuus3xRhKC7VOrO-uHAhTx7sPBbzCMUXuAcXthP4uVC-L7pRRWVmiPaPmm3wq7fbGRd6eJxj9l9545a0Kl2Ytg4eIb1HbwflEnx4Ok_Q729ff3U_yuuf36-6i-vSVBWdS8EYVpppQ0iL1WCI0LoBzVvKa62E4j0DaCmQgQ-K6bbpMfCaG16zhmiq2Qk63-duFz1Bb_LOUTm5jXZScSeDsvJfxdtRbsK9bHjVNG2TA86eAmK4WyDNcrLJgHPKQ1iSpFQwjOuKkIySPWpiSCnC8PIMwXKtTO4rk7kyuVYm1_jT1_u9OJ47ygDdAylLfgNR3oYl-vxn_0n9C_bLpZs</recordid><startdate>20190916</startdate><enddate>20190916</enddate><creator>Jakab, Géza</creator><creator>Bogdán, Dóra</creator><creator>Mazák, Károly</creator><creator>Deme, Ruth</creator><creator>Mucsi, Zoltán</creator><creator>Mándity, István M.</creator><creator>Noszál, Béla</creator><creator>Kállai-Szabó, Nikolett</creator><creator>Antal, István</creator><general>Springer International Publishing</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190916</creationdate><title>Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes</title><author>Jakab, Géza ; Bogdán, Dóra ; Mazák, Károly ; Deme, Ruth ; Mucsi, Zoltán ; Mándity, István M. ; Noszál, Béla ; Kállai-Szabó, Nikolett ; Antal, István</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-9330ab3bc1180afc19bb6eb78275ba9a7d3ee82e1f7fa3b86d0e757c75361b2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antineoplastic Agents, Phytogenic - administration & dosage</topic><topic>Antineoplastic Agents, Phytogenic - chemistry</topic><topic>Biochemistry</topic><topic>Biological Availability</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cyclodextrins - chemistry</topic><topic>Drug Delivery Systems</topic><topic>Flavonoids - administration & dosage</topic><topic>Flavonoids - chemistry</topic><topic>Lipids - chemistry</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Models, Molecular</topic><topic>Permeability</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Research Article</topic><topic>Solubility</topic><topic>Thermodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jakab, Géza</creatorcontrib><creatorcontrib>Bogdán, Dóra</creatorcontrib><creatorcontrib>Mazák, Károly</creatorcontrib><creatorcontrib>Deme, Ruth</creatorcontrib><creatorcontrib>Mucsi, Zoltán</creatorcontrib><creatorcontrib>Mándity, István M.</creatorcontrib><creatorcontrib>Noszál, Béla</creatorcontrib><creatorcontrib>Kállai-Szabó, Nikolett</creatorcontrib><creatorcontrib>Antal, István</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>AAPS PharmSciTech</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jakab, Géza</au><au>Bogdán, Dóra</au><au>Mazák, Károly</au><au>Deme, Ruth</au><au>Mucsi, Zoltán</au><au>Mándity, István M.</au><au>Noszál, Béla</au><au>Kállai-Szabó, Nikolett</au><au>Antal, István</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes</atitle><jtitle>AAPS PharmSciTech</jtitle><stitle>AAPS PharmSciTech</stitle><addtitle>AAPS PharmSciTech</addtitle><date>2019-09-16</date><risdate>2019</risdate><volume>20</volume><issue>8</issue><spage>314</spage><epage>314</epage><pages>314-314</pages><artnum>314</artnum><issn>1530-9932</issn><eissn>1530-9932</eissn><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 (log
P
) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility,
1
H/
13
C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (
P
app
= 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.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>31529175</pmid><doi>10.1208/s12249-019-1525-6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Antineoplastic Agents, Phytogenic - administration & dosage Antineoplastic Agents, Phytogenic - chemistry Biochemistry Biological Availability Biomedical and Life Sciences Biomedicine Biotechnology Cyclodextrins - chemistry Drug Delivery Systems Flavonoids - administration & dosage Flavonoids - chemistry Lipids - chemistry Magnetic Resonance Spectroscopy Models, Molecular Permeability Pharmacology/Toxicology Pharmacy Research Article Solubility Thermodynamics |
| title | Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes |
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