Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility
Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipien...
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| Veröffentlicht in: | AAPS PharmSciTech 2011-12, Vol.12 (4), p.1248-1263 |
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| creator | Wu, Yongmei Levons, Jaquan Narang, Ajit S. Raghavan, Krishnaswamy Rao, Venkatramana M. |
| description | Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipients for these impurities and a thorough understanding of their potential interaction with drug candidates during early formulation development ensure robust drug product development. In this review paper, excipient impurities are categorized into six major classes, including reducing sugars, aldehydes, peroxides, metals, nitrate/nitrite, and organic acids. The sources of generation, the analytical method for detection, the stability of impurities upon storage and processing, and the potential reactions with drug candidates of these impurities are reviewed. Specific examples of drug–excipient impurity interaction from internal research and literature are provided. Mitigation strategies and corrective measures are also discussed. |
| doi_str_mv | 10.1208/s12249-011-9677-z |
| format | Article |
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The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipients for these impurities and a thorough understanding of their potential interaction with drug candidates during early formulation development ensure robust drug product development. In this review paper, excipient impurities are categorized into six major classes, including reducing sugars, aldehydes, peroxides, metals, nitrate/nitrite, and organic acids. The sources of generation, the analytical method for detection, the stability of impurities upon storage and processing, and the potential reactions with drug candidates of these impurities are reviewed. Specific examples of drug–excipient impurity interaction from internal research and literature are provided. Mitigation strategies and corrective measures are also discussed.</description><identifier>ISSN: 1530-9932</identifier><identifier>EISSN: 1530-9932</identifier><identifier>DOI: 10.1208/s12249-011-9677-z</identifier><identifier>PMID: 21948318</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Chemistry, Pharmaceutical ; Drug Compounding ; Drug Contamination ; Drug Stability ; Drug-Related Side Effects and Adverse Reactions ; Excipients - chemistry ; Indexing in process ; Models, Chemical ; Pharmaceutical Preparations - chemistry ; Pharmacology/Toxicology ; Pharmacy ; Review ; Review Article ; Technology, Pharmaceutical - methods</subject><ispartof>AAPS PharmSciTech, 2011-12, Vol.12 (4), p.1248-1263</ispartof><rights>American Association of Pharmaceutical Scientists 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-6129c853d645211886fcfee018ee65c21ed4b6177509ecccc90205ddd29ffd9b3</citedby><cites>FETCH-LOGICAL-c540t-6129c853d645211886fcfee018ee65c21ed4b6177509ecccc90205ddd29ffd9b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225520/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225520/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21948318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Yongmei</creatorcontrib><creatorcontrib>Levons, Jaquan</creatorcontrib><creatorcontrib>Narang, Ajit S.</creatorcontrib><creatorcontrib>Raghavan, Krishnaswamy</creatorcontrib><creatorcontrib>Rao, Venkatramana M.</creatorcontrib><title>Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility</title><title>AAPS PharmSciTech</title><addtitle>AAPS PharmSciTech</addtitle><addtitle>AAPS PharmSciTech</addtitle><description>Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipients for these impurities and a thorough understanding of their potential interaction with drug candidates during early formulation development ensure robust drug product development. In this review paper, excipient impurities are categorized into six major classes, including reducing sugars, aldehydes, peroxides, metals, nitrate/nitrite, and organic acids. The sources of generation, the analytical method for detection, the stability of impurities upon storage and processing, and the potential reactions with drug candidates of these impurities are reviewed. Specific examples of drug–excipient impurity interaction from internal research and literature are provided. Mitigation strategies and corrective measures are also discussed.</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Chemistry, Pharmaceutical</subject><subject>Drug Compounding</subject><subject>Drug Contamination</subject><subject>Drug Stability</subject><subject>Drug-Related Side Effects and Adverse Reactions</subject><subject>Excipients - chemistry</subject><subject>Indexing in process</subject><subject>Models, Chemical</subject><subject>Pharmaceutical Preparations - chemistry</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Review</subject><subject>Review Article</subject><subject>Technology, Pharmaceutical - methods</subject><issn>1530-9932</issn><issn>1530-9932</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu1TAQtRCIPuAD2CAvWRDwjOPcmAUSKi1cqQiEYG3l-hFcJXawk4p2xT_wh3wJrlKuygZvxuPz8GgOIU-AvQBk7csMiLWsGEAlm82mur5HDkFwVknJ8f6d-wE5yvmCMeQg-UNygCDrlkN7SOJn2-nZX1q6Hacl-dnbTH2gpz-0n7wNc35FP6Xo_OBD_5xuTXnyzutu9jHQLhj6oWj6tY2Ovk1L__vnr72cboOO41TwXbGYrx6RB64bsn18W4_J17PTLyfvq_OP77Ynb84rLWo2Vw2g1K3gpqkFArRt47SzlkFrbSM0gjX1roHNRjBpdTmSIRPGGJTOGbnjx-T16jstu9EaXUZJ3aCm5McuXanYefUvEvw31cdLxRGFQFYMnt0apPh9sXlWo8_aDkMXbFyyAkCBXDQNL1RYqTrFnJN1-2-AqZug1BqUKkGpm6DUddE8vTvfXvE3mULAlZALFHqb1EVcUig7-4_rHw0-o0I</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Wu, Yongmei</creator><creator>Levons, Jaquan</creator><creator>Narang, Ajit S.</creator><creator>Raghavan, Krishnaswamy</creator><creator>Rao, Venkatramana M.</creator><general>Springer US</general><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20111201</creationdate><title>Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility</title><author>Wu, Yongmei ; Levons, Jaquan ; Narang, Ajit S. ; Raghavan, Krishnaswamy ; Rao, Venkatramana M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-6129c853d645211886fcfee018ee65c21ed4b6177509ecccc90205ddd29ffd9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Chemistry, Pharmaceutical</topic><topic>Drug Compounding</topic><topic>Drug Contamination</topic><topic>Drug Stability</topic><topic>Drug-Related Side Effects and Adverse Reactions</topic><topic>Excipients - chemistry</topic><topic>Indexing in process</topic><topic>Models, Chemical</topic><topic>Pharmaceutical Preparations - chemistry</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Review</topic><topic>Review Article</topic><topic>Technology, Pharmaceutical - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Yongmei</creatorcontrib><creatorcontrib>Levons, Jaquan</creatorcontrib><creatorcontrib>Narang, Ajit S.</creatorcontrib><creatorcontrib>Raghavan, Krishnaswamy</creatorcontrib><creatorcontrib>Rao, Venkatramana M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Wu, Yongmei</au><au>Levons, Jaquan</au><au>Narang, Ajit S.</au><au>Raghavan, Krishnaswamy</au><au>Rao, Venkatramana M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility</atitle><jtitle>AAPS PharmSciTech</jtitle><stitle>AAPS PharmSciTech</stitle><addtitle>AAPS PharmSciTech</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>12</volume><issue>4</issue><spage>1248</spage><epage>1263</epage><pages>1248-1263</pages><issn>1530-9932</issn><eissn>1530-9932</eissn><abstract>Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. 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| subjects | Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Chemistry, Pharmaceutical Drug Compounding Drug Contamination Drug Stability Drug-Related Side Effects and Adverse Reactions Excipients - chemistry Indexing in process Models, Chemical Pharmaceutical Preparations - chemistry Pharmacology/Toxicology Pharmacy Review Review Article Technology, Pharmaceutical - methods |
| title | Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility |
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