Liquid–liquid phase separation in pharmaceutical crystallization
[Display omitted] •A brief introduction of theories related to liquid–liquid phase separation.•Phase diagrams and measurement techniques of representative model systems.•Strategies to suppress liquid–liquid phase separation in crystallization.•Crystallization development in the presence of liquid–li...
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Veröffentlicht in: | Chemical engineering research & design 2021-10, Vol.174, p.19-29 |
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creator | Yu, Zai-Qun Zhang, Fang-Kun Tan, Reginald Beng Hee |
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•A brief introduction of theories related to liquid–liquid phase separation.•Phase diagrams and measurement techniques of representative model systems.•Strategies to suppress liquid–liquid phase separation in crystallization.•Crystallization development in the presence of liquid–liquid phase separation.•Options for indirect crystallization when liquid–liquid phase separation occurs.
Liquid–liquid phase separation (LLPS) during crystallization development of pharmaceuticals is being reported increasingly in recent years. It often causes quality issues such as failure of impurity reject and fragile morphology. In worst cases, crystallization cannot proceed at all after LLPS occurs. Many studies have been published on LLPS during crystallization and an analysis and synthesis of the current state-of-art is needed. In this review, recent advances in LLPS research will be summarized, including brief theoretical interpretations of LLPS, characteristics in phase diagrams and measurement methods for representative model systems, strategies to suppress LLPS, crystallization development in the presence of LLPS and options when direct crystallization fails due to LLPS. This review aims to provide a framework to deal with the occurrence of LLPS during crystallization development. |
doi_str_mv | 10.1016/j.cherd.2021.07.028 |
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•A brief introduction of theories related to liquid–liquid phase separation.•Phase diagrams and measurement techniques of representative model systems.•Strategies to suppress liquid–liquid phase separation in crystallization.•Crystallization development in the presence of liquid–liquid phase separation.•Options for indirect crystallization when liquid–liquid phase separation occurs.
Liquid–liquid phase separation (LLPS) during crystallization development of pharmaceuticals is being reported increasingly in recent years. It often causes quality issues such as failure of impurity reject and fragile morphology. In worst cases, crystallization cannot proceed at all after LLPS occurs. Many studies have been published on LLPS during crystallization and an analysis and synthesis of the current state-of-art is needed. In this review, recent advances in LLPS research will be summarized, including brief theoretical interpretations of LLPS, characteristics in phase diagrams and measurement methods for representative model systems, strategies to suppress LLPS, crystallization development in the presence of LLPS and options when direct crystallization fails due to LLPS. This review aims to provide a framework to deal with the occurrence of LLPS during crystallization development.</description><identifier>ISSN: 0263-8762</identifier><identifier>EISSN: 1744-3563</identifier><identifier>DOI: 10.1016/j.cherd.2021.07.028</identifier><language>eng</language><publisher>Rugby: Elsevier Ltd</publisher><subject>Chemical engineering ; Chemical synthesis ; Crystallization ; Liquid phases ; Liquid–liquid phase separation ; Measurement methods ; Morphology ; Pharmaceutical industry ; Pharmaceuticals ; Phase diagram ; Phase diagrams ; Phase separation ; Phase transitions ; Seeding ; Supersaturation control</subject><ispartof>Chemical engineering research & design, 2021-10, Vol.174, p.19-29</ispartof><rights>2021 Institution of Chemical Engineers</rights><rights>Copyright Elsevier Science Ltd. Oct 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-a42cfed285258e75fd99f19d0a053cc2579f2b42f4d08856841c51620ba821383</citedby><cites>FETCH-LOGICAL-c331t-a42cfed285258e75fd99f19d0a053cc2579f2b42f4d08856841c51620ba821383</cites><orcidid>0000-0002-4059-2069 ; 0000-0002-3352-4711</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cherd.2021.07.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Yu, Zai-Qun</creatorcontrib><creatorcontrib>Zhang, Fang-Kun</creatorcontrib><creatorcontrib>Tan, Reginald Beng Hee</creatorcontrib><title>Liquid–liquid phase separation in pharmaceutical crystallization</title><title>Chemical engineering research & design</title><description>[Display omitted]
•A brief introduction of theories related to liquid–liquid phase separation.•Phase diagrams and measurement techniques of representative model systems.•Strategies to suppress liquid–liquid phase separation in crystallization.•Crystallization development in the presence of liquid–liquid phase separation.•Options for indirect crystallization when liquid–liquid phase separation occurs.
Liquid–liquid phase separation (LLPS) during crystallization development of pharmaceuticals is being reported increasingly in recent years. It often causes quality issues such as failure of impurity reject and fragile morphology. In worst cases, crystallization cannot proceed at all after LLPS occurs. Many studies have been published on LLPS during crystallization and an analysis and synthesis of the current state-of-art is needed. In this review, recent advances in LLPS research will be summarized, including brief theoretical interpretations of LLPS, characteristics in phase diagrams and measurement methods for representative model systems, strategies to suppress LLPS, crystallization development in the presence of LLPS and options when direct crystallization fails due to LLPS. This review aims to provide a framework to deal with the occurrence of LLPS during crystallization development.</description><subject>Chemical engineering</subject><subject>Chemical synthesis</subject><subject>Crystallization</subject><subject>Liquid phases</subject><subject>Liquid–liquid phase separation</subject><subject>Measurement methods</subject><subject>Morphology</subject><subject>Pharmaceutical industry</subject><subject>Pharmaceuticals</subject><subject>Phase diagram</subject><subject>Phase diagrams</subject><subject>Phase separation</subject><subject>Phase transitions</subject><subject>Seeding</subject><subject>Supersaturation control</subject><issn>0263-8762</issn><issn>1744-3563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOwzAQRS0EEqXwBWwisU4Y2_EjCxZQ8ZIqsYG15fqhOkqT1E6QYMU_8Id8CWnLmtWMZu6dqzkIXWIoMGB-XRdm7aItCBBcgCiAyCM0w6Isc8o4PUYzIJzmUnByis5SqgFg2soZuluG7Rjsz9d3s2-yfq2Ty5LrddRD6NostLtZ3GjjxiEY3WQmfqRBN0343CvO0YnXTXIXf3WO3h7uXxdP-fLl8Xlxu8wNpXjIdUmMd5ZIRph0gnlbVR5XFjQwagxhovJkVRJfWpCScVliwzAnsNKSYCrpHF0d7vax244uDaruxthOkYpwgEowzumkogeViV1K0XnVx7DR8UNhUDtYqlZ7WGoHS4FQE6zJdXNwuemB9-CiSia41jgbojODsl341_8Ltj90UQ</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Yu, Zai-Qun</creator><creator>Zhang, Fang-Kun</creator><creator>Tan, Reginald Beng Hee</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8FD</scope><scope>JG9</scope><orcidid>https://orcid.org/0000-0002-4059-2069</orcidid><orcidid>https://orcid.org/0000-0002-3352-4711</orcidid></search><sort><creationdate>202110</creationdate><title>Liquid–liquid phase separation in pharmaceutical crystallization</title><author>Yu, Zai-Qun ; Zhang, Fang-Kun ; Tan, Reginald Beng Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-a42cfed285258e75fd99f19d0a053cc2579f2b42f4d08856841c51620ba821383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Chemical engineering</topic><topic>Chemical synthesis</topic><topic>Crystallization</topic><topic>Liquid phases</topic><topic>Liquid–liquid phase separation</topic><topic>Measurement methods</topic><topic>Morphology</topic><topic>Pharmaceutical industry</topic><topic>Pharmaceuticals</topic><topic>Phase diagram</topic><topic>Phase diagrams</topic><topic>Phase separation</topic><topic>Phase transitions</topic><topic>Seeding</topic><topic>Supersaturation control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Zai-Qun</creatorcontrib><creatorcontrib>Zhang, Fang-Kun</creatorcontrib><creatorcontrib>Tan, Reginald Beng Hee</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><jtitle>Chemical engineering research & design</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Zai-Qun</au><au>Zhang, Fang-Kun</au><au>Tan, Reginald Beng Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liquid–liquid phase separation in pharmaceutical crystallization</atitle><jtitle>Chemical engineering research & design</jtitle><date>2021-10</date><risdate>2021</risdate><volume>174</volume><spage>19</spage><epage>29</epage><pages>19-29</pages><issn>0263-8762</issn><eissn>1744-3563</eissn><abstract>[Display omitted]
•A brief introduction of theories related to liquid–liquid phase separation.•Phase diagrams and measurement techniques of representative model systems.•Strategies to suppress liquid–liquid phase separation in crystallization.•Crystallization development in the presence of liquid–liquid phase separation.•Options for indirect crystallization when liquid–liquid phase separation occurs.
Liquid–liquid phase separation (LLPS) during crystallization development of pharmaceuticals is being reported increasingly in recent years. It often causes quality issues such as failure of impurity reject and fragile morphology. In worst cases, crystallization cannot proceed at all after LLPS occurs. Many studies have been published on LLPS during crystallization and an analysis and synthesis of the current state-of-art is needed. In this review, recent advances in LLPS research will be summarized, including brief theoretical interpretations of LLPS, characteristics in phase diagrams and measurement methods for representative model systems, strategies to suppress LLPS, crystallization development in the presence of LLPS and options when direct crystallization fails due to LLPS. This review aims to provide a framework to deal with the occurrence of LLPS during crystallization development.</abstract><cop>Rugby</cop><pub>Elsevier Ltd</pub><doi>10.1016/j.cherd.2021.07.028</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4059-2069</orcidid><orcidid>https://orcid.org/0000-0002-3352-4711</orcidid></addata></record> |
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subjects | Chemical engineering Chemical synthesis Crystallization Liquid phases Liquid–liquid phase separation Measurement methods Morphology Pharmaceutical industry Pharmaceuticals Phase diagram Phase diagrams Phase separation Phase transitions Seeding Supersaturation control |
title | Liquid–liquid phase separation in pharmaceutical crystallization |
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