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Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer
Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvem...
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| Published in: | Biological & pharmaceutical bulletin 2019/06/01, Vol.42(6), pp.1004-1012 |
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| creator | Suzuki, Yumena Muangnoi, Chawanphat Thaweesest, Wuttinont Teerawonganan, Polsak Bhuket, Pahweenvaj Ratnatilaka Na Titapiwatanakun, Varin Yoshimura-Fujii, Mika Sritularak, Boonchoo Likhitwitayawuid, Kittisak Rojsitthisak, Pornchai Fukami, Toshiro |
| description | Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm−1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV. |
| doi_str_mv | 10.1248/bpb.b19-00048 |
| format | article |
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However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm−1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b19-00048</identifier><identifier>PMID: 31155574</identifier><language>eng ; jpn</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Acetic acid ; Bioavailability ; Caco-2 cell monolayer ; Carboxylic acids ; characterization ; Citric acid ; cocrystal ; Cytotoxicity ; Dissolution ; Ethyl acetate ; Evaporation ; Grinding ; Membrane permeability ; oxyresveratrol ; Permeability ; Raman spectroscopy ; Slurries ; Solubility ; Thermal analysis</subject><ispartof>Biological and Pharmaceutical Bulletin, 2019/06/01, Vol.42(6), pp.1004-1012</ispartof><rights>2019 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-92285d8452c858a7b494f66f00ec5065eeb7d99a8899c1e4a73477b114c4419f3</citedby><cites>FETCH-LOGICAL-c702t-92285d8452c858a7b494f66f00ec5065eeb7d99a8899c1e4a73477b114c4419f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31155574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Yumena</creatorcontrib><creatorcontrib>Muangnoi, Chawanphat</creatorcontrib><creatorcontrib>Thaweesest, Wuttinont</creatorcontrib><creatorcontrib>Teerawonganan, Polsak</creatorcontrib><creatorcontrib>Bhuket, Pahweenvaj Ratnatilaka Na</creatorcontrib><creatorcontrib>Titapiwatanakun, Varin</creatorcontrib><creatorcontrib>Yoshimura-Fujii, Mika</creatorcontrib><creatorcontrib>Sritularak, Boonchoo</creatorcontrib><creatorcontrib>Likhitwitayawuid, Kittisak</creatorcontrib><creatorcontrib>Rojsitthisak, Pornchai</creatorcontrib><creatorcontrib>Fukami, Toshiro</creatorcontrib><creatorcontrib>bNatural Products for Ageing and Chronic Diseases Research Unit</creatorcontrib><creatorcontrib>cFaculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>Chulalongkorn University</creatorcontrib><creatorcontrib>Meiji Pharmaceutical University</creatorcontrib><creatorcontrib>aDepartment of Molecular Pharmaceutics</creatorcontrib><title>Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm−1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.</description><subject>Acetic acid</subject><subject>Bioavailability</subject><subject>Caco-2 cell monolayer</subject><subject>Carboxylic acids</subject><subject>characterization</subject><subject>Citric acid</subject><subject>cocrystal</subject><subject>Cytotoxicity</subject><subject>Dissolution</subject><subject>Ethyl acetate</subject><subject>Evaporation</subject><subject>Grinding</subject><subject>Membrane permeability</subject><subject>oxyresveratrol</subject><subject>Permeability</subject><subject>Raman spectroscopy</subject><subject>Slurries</subject><subject>Solubility</subject><subject>Thermal analysis</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkUFr3DAQhUVpaLZpj70WQS-5OJFkyZaOwWzSQNIE0p6FrB0nXmRpK9khhv74aneTLfQyAs3HmzfzEPpCyRllXJ63m_aspaoghHD5Di1oyetCMCreowVRVBYVFfIYfUxpnZGasPIDOi4pFULUfIH-LF82LsTeP-If4RkcboKNcxqNc70HfBnikHDo8N3LHCE9QzRjDA6PAS_9k_EW8MXvCcKU8ENwU9u7fpyx8St8D3EA8_ZhY0gJG9yAc_g2-ODMDPETOuqMS_D59T1Bvy6XP5vvxc3d1XVzcVPY7HcsFGNSrCQXzEohTd1yxbuq6ggBK0glANp6pZSRUilLgZs636BuKeWWc6q68gSd7nU3MWS3adRDn2y2YvzWumas5FxWtCoz-u0_dB2m6LO7TPF8XElrlqliT-32itDpTewHE2dNid7GonMsOseid7Fk_uur6tQOsDrQbzlk4GoP5G5vjQt-e_5_s22q2z64oBnZiXJGKk0YzfMIz4WykinGS5GVmr3SOof4CIdRJo69dbAzxpmutuVg8NC1TyZq8OVfcQq3Og</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Suzuki, Yumena</creator><creator>Muangnoi, Chawanphat</creator><creator>Thaweesest, Wuttinont</creator><creator>Teerawonganan, Polsak</creator><creator>Bhuket, Pahweenvaj Ratnatilaka Na</creator><creator>Titapiwatanakun, Varin</creator><creator>Yoshimura-Fujii, Mika</creator><creator>Sritularak, Boonchoo</creator><creator>Likhitwitayawuid, Kittisak</creator><creator>Rojsitthisak, Pornchai</creator><creator>Fukami, Toshiro</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20190601</creationdate><title>Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer</title><author>Suzuki, Yumena ; 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However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm−1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>31155574</pmid><doi>10.1248/bpb.b19-00048</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0918-6158 |
| ispartof | Biological and Pharmaceutical Bulletin, 2019/06/01, Vol.42(6), pp.1004-1012 |
| issn | 0918-6158 1347-5215 |
| language | eng ; jpn |
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| source | Full-Text Journals in Chemistry (Open access) |
| subjects | Acetic acid Bioavailability Caco-2 cell monolayer Carboxylic acids characterization Citric acid cocrystal Cytotoxicity Dissolution Ethyl acetate Evaporation Grinding Membrane permeability oxyresveratrol Permeability Raman spectroscopy Slurries Solubility Thermal analysis |
| title | Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer |
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