{"id":"https://openalex.org/W2060163502","doi":"https://doi.org/10.5731/pdajpst.2012.00861","title":"Investigation of Freeze/Thaw-Related Quality Attributes of a Liquid Biopharmaceutical Formulation: The Role of Saccharide Excipients","display_name":"Investigation of Freeze/Thaw-Related Quality Attributes of a Liquid Biopharmaceutical Formulation: The Role of Saccharide Excipients","publication_year":2012,"publication_date":"2012-05-01","ids":{"openalex":"https://openalex.org/W2060163502","doi":"https://doi.org/10.5731/pdajpst.2012.00861","mag":"2060163502","pmid":"https://pubmed.ncbi.nlm.nih.gov/22634588"},"language":"en","primary_location":{"id":"doi:10.5731/pdajpst.2012.00861","doi":"https://doi.org/10.5731/pdajpst.2012.00861","is_oa":false,"landing_page_url":"https://doi.org/10.5731/pdajpst.2012.00861","pdf_url":null,"source":{"id":"https://openalex.org/S21493941","display_name":"PDA Journal of Pharmaceutical Science and Technology","issn_l":"1079-7440","issn":["1079-7440","1948-2124"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","jufo-1","medline","norway-1","poland-70","russia-white-list-3"],"host_organization":"https://openalex.org/P4360969396","host_organization_name":"Parenteral Drug Association","host_organization_lineage":["https://openalex.org/P4360969396"],"host_organization_lineage_names":["Parenteral Drug Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PDA Journal of Pharmaceutical Science and Technology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5069305433","display_name":"Rong Zhou","orcid":"https://orcid.org/0000-0003-4018-381X","observed_orcids":["https://orcid.org/0000-0003-4018-381X"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R. Zhou","raw_affiliation_strings":["Department of Drug Product Science & Technology, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, NJ 08903"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Drug Product Science & Technology, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, NJ 08903","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003142213","display_name":"Roxana F. Schlam","orcid":"https://orcid.org/0000-0003-3322-1750","observed_orcids":["https://orcid.org/0000-0003-3322-1750"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"R. F. Schlam","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113882736","display_name":"Shawn X. Yin","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"S. Yin","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080113590","display_name":"Rajesh B. Gandhi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"R. B. Gandhi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5109392421","display_name":"Michael L. Adams","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"M. L. Adams","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":3,"citation_normalized_percentile":{"value":0.11134416,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":95},"biblio":{"volume":"66","issue":"3","first_page":"221","last_page":"235"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11124","display_name":"Protein purification and stability","score":0.9336000084877014,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11124","display_name":"Protein purification and stability","score":0.9336000084877014,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T14479","display_name":"Freezing and Crystallization Processes","score":0.03530000150203705,"subfield":{"id":"https://openalex.org/subfields/2211","display_name":"Mechanics of Materials"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11881","display_name":"Crystallization and Solubility Studies","score":0.01720000058412552,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/freeze-thaw-behavior","display_name":"freeze-thaw behavior","score":0.7440000176429749},{"id":"https://openalex.org/keywords/mannitol","display_name":"mannitol","score":0.9169999957084656},{"id":"https://openalex.org/keywords/sucrose","display_name":"sucrose","score":0.6949999928474426},{"id":"https://openalex.org/keywords/trehalose","display_name":"trehalose","score":1.0},{"id":"https://openalex.org/keywords/sorbitol","display_name":"sorbitol","score":1.0},{"id":"https://openalex.org/keywords/osmolality","display_name":"osmolality","score":0.6859999895095825},{"id":"https://openalex.org/keywords/scale-up-effects","display_name":"scale-up effects","score":0.5419999957084656},{"id":"https://openalex.org/keywords/cryoprotectants","display_name":"cryoprotectants","score":0.7649999856948853},{"id":"https://openalex.org/keywords/storage-conditions","display_name":"storage conditions","score":0.35600000619888306},{"id":"https://openalex.org/keywords/excipient-selection","display_name":"excipient selection","score":0.5479999780654907}],"concepts":[{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.7150341272354126},{"id":"https://openalex.org/C17971392","wikidata":"https://www.wikidata.org/wiki/Q18027445","display_name":"5-HT5A receptor","level":3,"score":0.7077701091766357},{"id":"https://openalex.org/C16232356","wikidata":"https://www.wikidata.org/wiki/Q4215980","display_name":"Raji cell","level":3,"score":0.592245876789093},{"id":"https://openalex.org/C116016267","wikidata":"https://www.wikidata.org/wiki/Q18039826","display_name":"Interleukin-21 receptor","level":3,"score":0.5851379632949829},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.5746353268623352},{"id":"https://openalex.org/C197462201","wikidata":"https://www.wikidata.org/wiki/Q2476074","display_name":"Cell surface receptor","level":3,"score":0.5661527514457703},{"id":"https://openalex.org/C125268873","wikidata":"https://www.wikidata.org/wiki/Q17918484","display_name":"Protease-activated receptor 2","level":4,"score":0.5556254982948303},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.49164706468582153},{"id":"https://openalex.org/C75184817","wikidata":"https://www.wikidata.org/wiki/Q5381540","display_name":"Enzyme-linked receptor","level":3,"score":0.48899757862091064},{"id":"https://openalex.org/C157695867","wikidata":"https://www.wikidata.org/wiki/Q1100474","display_name":"B-cell receptor","level":4,"score":0.47744303941726685},{"id":"https://openalex.org/C2993002077","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Receptor expression","level":3,"score":0.44405287504196167},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.4365572929382324},{"id":"https://openalex.org/C98654944","wikidata":"https://www.wikidata.org/wiki/Q14885185","display_name":"Common gamma chain","level":4,"score":0.41652360558509827},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.4088369607925415},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.38282012939453125},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3766182065010071},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3679935038089752},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3021107316017151},{"id":"https://openalex.org/C2778453870","wikidata":"https://www.wikidata.org/wiki/Q188930","display_name":"B cell","level":3,"score":0.1856096386909485},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.12160074710845947},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.06451091170310974},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002152","descriptor_name":"Calorimetry, Differential Scanning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002626","descriptor_name":"Chemistry, Pharmaceutical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005079","descriptor_name":"Excipients","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D005612","descriptor_name":"Freeze Drying","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D005615","descriptor_name":"Freezing","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008353","descriptor_name":"Mannitol","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013395","descriptor_name":"Sucrose","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.5731/pdajpst.2012.00861","doi":"https://doi.org/10.5731/pdajpst.2012.00861","is_oa":false,"landing_page_url":"https://doi.org/10.5731/pdajpst.2012.00861","pdf_url":null,"source":{"id":"https://openalex.org/S21493941","display_name":"PDA Journal of Pharmaceutical Science and Technology","issn_l":"1079-7440","issn":["1079-7440","1948-2124"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","jufo-1","medline","norway-1","poland-70","russia-white-list-3"],"host_organization":"https://openalex.org/P4360969396","host_organization_name":"Parenteral Drug Association","host_organization_lineage":["https://openalex.org/P4360969396"],"host_organization_lineage_names":["Parenteral Drug Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PDA Journal of Pharmaceutical Science and Technology","raw_type":"journal-article"},{"id":"pmid:22634588","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/22634588","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PDA journal of pharmaceutical science and technology","raw_type":"Journal Article"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.895.6917","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.895.6917","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"https://www.researchgate.net/profile/Rong_Zhou/publication/225064002_Investigation_of_freezethaw-related_quality_attributes_of_a_liquid_biopharmaceutical_formulation_the_role_of_saccharide_excipients/links/0fcfd4fe8ac45c8784000000.pdf","raw_type":"text"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320307115","display_name":"Bristol-Myers Squibb","ror":"https://ror.org/00gtmwv55"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":33,"referenced_works":["https://openalex.org/W25381815","https://openalex.org/W164496576","https://openalex.org/W309309890","https://openalex.org/W1276324155","https://openalex.org/W1454256324","https://openalex.org/W1483067299","https://openalex.org/W1532747786","https://openalex.org/W1555994455","https://openalex.org/W1802213410","https://openalex.org/W1841200799","https://openalex.org/W1967889181","https://openalex.org/W1970898345","https://openalex.org/W1981286439","https://openalex.org/W1984655166","https://openalex.org/W2005517133","https://openalex.org/W2012061934","https://openalex.org/W2038052574","https://openalex.org/W2048016595","https://openalex.org/W2065823682","https://openalex.org/W2070399131","https://openalex.org/W2076995834","https://openalex.org/W2113306739","https://openalex.org/W2118107894","https://openalex.org/W2153585226","https://openalex.org/W2155886309","https://openalex.org/W2272041574","https://openalex.org/W2321347883","https://openalex.org/W2337029126","https://openalex.org/W2342186566","https://openalex.org/W2415517649","https://openalex.org/W2479156638","https://openalex.org/W2502592889","https://openalex.org/W4285719527"],"related_works":["https://openalex.org/W7095257059","https://openalex.org/W2014351688","https://openalex.org/W2565839488","https://openalex.org/W2272041574","https://openalex.org/W1841200799","https://openalex.org/W2342186566","https://openalex.org/W4284960592","https://openalex.org/W2962788378","https://openalex.org/W1972934366","https://openalex.org/W2017787797"],"abstract_inverted_index":{"Saccharides,":[0,295],"including":[1,83,240,296,400],"sucrose,":[2,242,297,402],"trehalose,":[3,244,298,404],"mannitol,":[4,236,299,396],"and":[5,94,138,219,243,262,286,300,403,422,446],"sorbitol,":[6,241,301,401],"are":[7,280,302,440],"commonly":[8,303],"employed":[9,304],"as":[10,305],"stabilizers,":[11,306],"cryoprotectants,":[12],"and/or":[13,308],"tonicity":[14,234,309,394],"adjusters":[15,310],"in":[16,131,149,216,311],"protein":[17,312],"formulations.":[18,104,292,313,363,452],"During":[19,314],"the":[20,65,70,74,103,139,145,150,156,165,225,229,233,273,349,362,385,389,393,433],"thawing":[21,315],"of":[22,67,73,108,118,141,144,184,195,232,254,316,351,369,379,392,414],"a":[23,32,38,119,128,251,321,380,411],"protein-containing":[24],"formulated":[25,317],"bulk":[26,113,318,374],"drug":[27,33,319,337],"substance":[28],"conducted":[29],"prior":[30],"to":[31,101,170,193,208,228,256,360,388,416],"product":[34,338],"(DP)":[35],"filling":[36],"operation,":[37],"white,":[39,322],"crystalline":[40,323],"precipitate":[41,109,324,370],"was":[42,50,77,114,270,325,333,375,430],"observed.":[43,326],"In":[44,176,327],"addition,":[45,177,328],"upon":[46,329],"thawing,":[47,330],"vial":[48,166,268,331,428],"breakage":[49,167,269,332,429],"observed":[51,125,173,197,271,334,431],"for":[52,272,277,289,335,432,437,449],"filled":[53,336],"DP":[54],"that":[55,117,155,188,339,378],"had":[56,340],"been":[57,341],"previously":[58,342],"frozen":[59,146,157,185,343],"at":[60,162,198,212,247,344,407],"-40":[61,345],"\u00b0C.":[62,346],"To":[63,347],"investigate":[64,348],"causes":[66,350],"both":[68,352],"phenomena,":[69,353],"freeze/thaw":[71,230,390],"behavior":[72,211,227,387],"formulation":[75],"components":[76],"studied.":[78],"Multiple":[79],"physical":[80,355],"characterization":[81,356],"techniques,":[82],"differential":[84],"scanning":[85],"calorimetry":[86],"(DSC),":[87],"electrical":[88,132],"resistance":[89,133],"measurements,":[90,137],"thermomechanical":[91],"analysis":[92],"(TMA),":[93],"powder":[95,365],"X-ray":[96,366],"diffraction":[97,367],"(PXRD),":[98],"were":[99,245,358,405],"utilized":[100,359],"characterize":[102,361],"The":[105,364],"PXRD":[106],"pattern":[107,368],"collected":[110,371],"from":[111,181,372],"thawed":[112,373],"consistent":[115,376],"with":[116,377],"mannitol":[120,158,196,381],"control.":[121,382],"An":[122],"exothermic":[123],"transition":[124],"by":[126],"DSC,":[127],"sharp":[129],"increase":[130],"detected":[134],"via":[135],"resistivity":[136],"onset":[140],"volumetric":[142],"expansion":[143],"matrix":[147],"evident":[148],"TMA":[151],"curve":[152],"offer":[153],"evidence":[154],"solution":[159],"undergoes":[160],"transitions":[161],"or":[163],"near":[164],"temperature":[168,252,412],"(-22":[169],"-23":[171],"\u00b0C)":[172],"during":[174],"warming.":[175],"osmolality":[178],"measurements":[179],"taken":[180],"fractionated":[182],"aliquots":[183],"samples":[186],"indicated":[187],"non-uniform":[189],"concentration":[190],"gradients":[191],"contributed":[192],"precipitation":[194,266,426],"larger":[199,213],"scales.":[200],"Small-scale":[201],"laboratory":[202],"experiments":[203],"(i.e.,":[204,215],"10-125":[205],"mL)":[206],"failed":[207],"adequately":[209],"predict":[210],"scale":[214,287,447],"1":[217],"L":[218,221],"2":[220],"bottles).":[222],"Upon":[223,383],"linking":[224,384],"detrimental":[226,386],"properties":[231,391],"adjustor,":[235,395],"alternative":[237,397],"saccharide":[238,278,398,438],"excipients,":[239,399],"evaluated":[246,406],"isotonic":[248,408],"concentrations":[249,409],"over":[250,410],"range":[253,413],"-80":[255,415],"25":[257,417],"\u00b0C":[258,418],"using":[259,419],"physical-chemical":[260],"techniques":[261,357,421],"visual":[263,423],"observation.":[264,424],"Neither":[265,425],"nor":[267,427],"alternate":[274,434],"saccharides.":[275,435],"Recommendations":[276,436],"selection":[279,439],"provided":[281],"based":[282,442],"on":[283,443],"storage":[284,444],"conditions":[285,445],"considerations":[288,448],"liquid":[290,450],"biopharmaceutical":[291,451],"LAY":[293],"ABSTRACT:":[294],"cryoprotectants":[307],"substance,":[320],"multiple":[354],"physico-chemical":[420],"given":[441]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}