The stability of insulin solutions in syringes is improved by ensuring lower molecular weight silicone lubricants are absent

Protein drugs such as insulin are almost universally delivered via glass syringes lubricated with silicone oil. It is not uncommon for prefilled syringes (PFS) to become cloudy, which may affect bioavailability or total drug dose. To examine the role, if any, of the silicone oil lubricant in this pr...

Full description

Saved in:
Bibliographic Details
Published inHeliyon Vol. 3; no. 3; p. e00264
Main Authors Nayef, Lamees, Khan, Madiha F., Brook, Michael A.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.03.2017
Elsevier
Subjects
Biochemistry
Bioengineering
Biotechnology
Inorganic chemistry
Organic chemistry
Bioengineering
Biotechnology
Organic chemistry
Biochemistry
Inorganic chemistry
Online AccessGet full text

Cover

Abstract Protein drugs such as insulin are almost universally delivered via glass syringes lubricated with silicone oil. It is not uncommon for prefilled syringes (PFS) to become cloudy, which may affect bioavailability or total drug dose. To examine the role, if any, of the silicone oil lubricant in this process, a systematic evaluation of the degree of insulin denaturation and aggregation as a function of silicone oils of different molecular weights was undertaken. The former was measured using fluorescence changes of aqueous insulin/silicone dispersions, while the latter examined changes in turbidity as a function of mixing and silicone oil type; the results were confirmed at two different insulin concentrations and agitation speeds. Lower molecular weight silicones led to the most rapid denaturation and aggregation, and when examined in blends of silicones at a fixed viscosity of 1000 cSt, commonly used for syringe lubrication, more rapid denaturation/aggregation was noted in blends of silicones containing the largest fractions of low molecular weight materials. As a consequence, the molecular weight profile of silicone lubricants should be established prior to the preparation of prefilled syringes.
AbstractList Protein drugs such as insulin are almost universally delivered via glass syringes lubricated with silicone oil. It is not uncommon for prefilled syringes (PFS) to become cloudy, which may affect bioavailability or total drug dose. To examine the role, if any, of the silicone oil lubricant in this process, a systematic evaluation of the degree of insulin denaturation and aggregation as a function of silicone oils of different molecular weights was undertaken. The former was measured using fluorescence changes of aqueous insulin/silicone dispersions, while the latter examined changes in turbidity as a function of mixing and silicone oil type; the results were confirmed at two different insulin concentrations and agitation speeds. Lower molecular weight silicones led to the most rapid denaturation and aggregation, and when examined in blends of silicones at a fixed viscosity of 1000 cSt, commonly used for syringe lubrication, more rapid denaturation/aggregation was noted in blends of silicones containing the largest fractions of low molecular weight materials. As a consequence, the molecular weight profile of silicone lubricants should be established prior to the preparation of prefilled syringes.
ArticleNumber e00264
Author Nayef, Lamees
Khan, Madiha F.
Brook, Michael A.
AuthorAffiliation b Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W., Hamilton, ON, L8S 4M1, Canada
a School of Biomedical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4M1, Canada
AuthorAffiliation_xml – name: b Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W., Hamilton, ON, L8S 4M1, Canada
– name: a School of Biomedical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4M1, Canada
Author_xml – sequence: 1
  givenname: Lamees
  surname: Nayef
  fullname: Nayef, Lamees
  organization: School of Biomedical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4M1, Canada
– sequence: 2
  givenname: Madiha F.
  surname: Khan
  fullname: Khan, Madiha F.
  organization: School of Biomedical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4M1, Canada
– sequence: 3
  givenname: Michael A.
  surname: Brook
  fullname: Brook, Michael A.
  email: mabrook@mcmaster.ca
  organization: School of Biomedical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4M1, Canada
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28367509$$D View this record in MEDLINE/PubMed
BookMark eNqFUk1vEzEQXaEiWkp_AshHLgn-3LUvIFRBqVSJSzlbXns2ceTYwd5NFYkfj9MNVXtCsuQZz5s3H35vm7OYIjTNe4KXBJP202a5huAPKS4pJt0SMKYtf9VcUI7FQnKOz57Z581VKRuMMRGyVR1705xTydpOYHXR_LlfAyqj6X3w4wGlAflYpuAjKilMo0-xoKNzyD6uoNr1bHc57cGh_oCggo8RFNIDZLRNAewUTEYP4FfrEZVKa2vvKEx99tbEsSCTAZm-QBzfNa8HEwpcne7L5tf3b_fXPxZ3P29ur7_eLaxgbFywoet4HaQFR4nihhnZY6cYFZ3sCAZRpxTEKTdw2bVqcK1gUnKBjXCtNIJdNrczr0tmo3fZb00-6GS8fnxIeaVNHr0NoJUDJ6Wj4AbgitreGgk95aAUcGd45fo8c-2mfgvO1jGyCS9IX0aiX-tV2mvBWkoEqQQfTwQ5_Z6gjHrri4UQTIQ0FU2kZJJTqdoKFTPU5lRKhuGpDMH6KAS90Sch6KMQ9CyEmvfheY9PWf--vQK-zACoW997yLpYD9GC8xnsWNfi_1PiLzxFzNc
CitedBy_id crossref_primary_10_1093_ajhp_zxab484
crossref_primary_10_1177_1932296819876924
crossref_primary_10_1515_pthp_2021_0005
crossref_primary_10_1016_j_xphs_2023_08_003
crossref_primary_10_1177_1932296820915875
crossref_primary_10_1039_D3CC03531J
crossref_primary_10_1097_MD_0000000000033983
crossref_primary_10_1515_pthp_2021_0014
crossref_primary_10_1177_19322968221112120
crossref_primary_10_1208_s12249_018_1184_z
crossref_primary_10_1016_j_ifacsc_2019_100042
crossref_primary_10_1097_MD_0000000000031812
crossref_primary_10_3390_pharmaceutics16050580
crossref_primary_10_1007_s11095_023_03633_7
crossref_primary_10_1002_cbic_202100678
Cites_doi 10.1002/jps.21982
10.1021/bm800226z
10.2337/diacare.10.6.786
10.1002/jps.24184
10.1002/jps.23434
10.1073/pnas.0910080106
10.1002/jps.23328
10.1017/S1431927608086807
10.1021/la025867k
10.1073/pnas.88.21.9377
10.3109/03639049509069255
10.1111/j.1399-3011.1990.tb01292.x
10.1016/j.bbapap.2010.04.001
10.1002/bit.260400805
10.1021/la0518997
10.1016/S0959-440X(98)80037-7
10.1529/biophysj.107.105338
10.2337/diacare.9.6.672
10.1021/jp903522e
10.1016/j.ab.2010.12.008
10.1089/dia.2009.0006
10.1002/jps.20321
10.1002/(SICI)1097-0134(199704)27:4<507::AID-PROT4>3.0.CO;2-7
10.1023/A:1013334916162
10.1016/j.pid.2013.11.005
10.1002/(SICI)1097-0290(19970620)54:6<503::AID-BIT1>3.0.CO;2-N
10.1016/S0142-9612(97)00105-1
10.3109/10611869308996093
10.1007/s11095-012-0696-6
10.1002/jps.20079
10.1016/j.colsurfb.2015.03.013
10.1002/jps.21719
10.1016/j.cocis.2007.07.010
10.1021/bi00171a010
10.1021/bi002555c
10.1586/erv.10.129
ContentType Journal Article
Copyright 2017 The Authors
2017 The Authors 2017
Copyright_xml – notice: 2017 The Authors
– notice: 2017 The Authors 2017
DBID 6I.
AAFTH
NPM
AAYXX
CITATION
7X8
5PM
DOA
DOI 10.1016/j.heliyon.2017.e00264
DatabaseName ScienceDirect Open Access Titles
Elsevier:ScienceDirect:Open Access
PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
Directory of Open Access Journals
DatabaseTitle PubMed
CrossRef
MEDLINE - Academic
DatabaseTitleList


PubMed
Database_xml – sequence: 1
  dbid: DOA
  name: Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 2405-8440
EndPage e00264
ExternalDocumentID oai_doaj_org_article_9ded88d2edfe492cbca8eb24e99e4da4
10_1016_j_heliyon_2017_e00264
28367509
S2405844016319594
Genre Journal Article
GroupedDBID 0R~
0SF
457
53G
5VS
6I.
AACTN
AAEDW
AAFTH
AAFWJ
ABMAC
ACGFS
ACLIJ
ADBBV
ADEZE
AEXQZ
AFPKN
AFTJW
AGHFR
AITUG
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
AOIJS
BAWUL
BCNDV
DIK
EBS
EJD
FDB
GROUPED_DOAJ
HYE
IPNFZ
KQ8
M~E
NCXOZ
O9-
OK1
RIG
ROL
RPM
SSZ
AALRI
ADVLN
AFJKZ
AKRWK
NPM
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c533t-3f7744406ed2194a3a8b0d932578710e584451d9df48769fd65388450a5d68a53
IEDL.DBID RPM
ISSN 2405-8440
IngestDate Tue Oct 22 15:13:13 EDT 2024
Tue Sep 17 21:20:34 EDT 2024
Fri Oct 25 07:32:07 EDT 2024
Thu Sep 26 17:22:54 EDT 2024
Tue Oct 15 23:55:36 EDT 2024
Tue Jul 25 20:51:25 EDT 2023
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 3
Keywords Bioengineering
Biotechnology
Organic chemistry
Biochemistry
Inorganic chemistry
Language English
License This is an open access article under the CC BY-NC-ND license.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c533t-3f7744406ed2194a3a8b0d932578710e584451d9df48769fd65388450a5d68a53
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362151/
PMID 28367509
PQID 1883842896
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_9ded88d2edfe492cbca8eb24e99e4da4
pubmedcentral_primary_oai_pubmedcentral_nih_gov_5362151
proquest_miscellaneous_1883842896
crossref_primary_10_1016_j_heliyon_2017_e00264
pubmed_primary_28367509
elsevier_sciencedirect_doi_10_1016_j_heliyon_2017_e00264
PublicationCentury 2000
PublicationDate 2017-03-01
PublicationDateYYYYMMDD 2017-03-01
PublicationDate_xml – month: 03
  year: 2017
  text: 2017-03-01
  day: 01
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Heliyon
PublicationTitleAlternate Heliyon
PublicationYear 2017
Publisher Elsevier Ltd
Elsevier
Publisher_xml – name: Elsevier Ltd
– name: Elsevier
References (bib0045) 2013
Jones, Kaufmann, Middaugh (bib0150) 2005; 94
Shire, Shahrokh, Liu (bib0015) 2004; 93
Bernstein (bib0115) 1987; 10
Woehl, Carre (bib0040) 2003; 3
Smith, Sharp, Roberts (bib0210) 2007; 93
Brange, Dodson, Edwards, Holden, Whittingham (bib0095) 1997; 27
Ludwig, Trotter, Gabrielson, Carpenter, Randolph (bib0110) 2011; 410
Dathe, Gast, Zirwer, Welfle, Mehlis (bib0125) 1990; 36
Krayukhina, Tsumoto, Uchiyama, Fukui (bib0120) 2015; 104
Kwon, Baudys, Knutson, Kim (bib0195) 2001; 18
Carré, Woehl (bib0030) 2006; 22
Basu, Krishnan, Thirumangalathu, Randolph, Carpenter (bib0065) 2013; 102
Zelisko, Flora, Brennan, Brook (bib0180) 2008; 9
Asakura, Seino, Nakano, Muto, Toraishi, Sako, Kageyama, Yohkoh (bib0005) 2009; 11
Dodson, Steiner (bib0185) 1998; 8
Biancalana, Koide (bib0190) 2010; 1804
Nielsen, Khurana, Coats, Frokjaer, Brange, Vyas, Uversky, Fink (bib0135) 2001; 40
Sluzky, Tamada, Klibanov, Langer (bib0155) 1991; 88
Chantelau, Berger, Böhlken (bib0215) 1986; 9
van der Linden, Venema (bib0075) 2007; 12
Rapra (bib0020) 2015
Noll (bib0035) 1968
Kasi, Prabhu, Sanjay, Chitkara, Mitra (bib0025) 2013; 5
Felsovalyi, Janvier, Jouffray, Soukiassian, Mangiagalli (bib0050) 2012; 101
Millican, Brems (bib0100) 1994; 33
Bekard, Dunstan (bib0140) 2009; 113
Sluzky, Klibanov, Langer (bib0160) 1992; 40
Thirumangalathu, Krishnan, Ricci, Brems, Randolph, Carpenter (bib0080) 2009; 98
Nayef, Khan, Brook (bib0170) 2015; 128
Ivanova, Sievers, Sawaya, Wall, Eisenberg (bib0200) 2009; 106
Amiji, Shah, Boroujerdi (bib0205) 1995; 21
Zelisko, Brook (bib0090) 2002; 18
Sun, Alexander, Lattarulo, Blumenthal, Ricci, Chen (bib0085) 1997; 18
Ludwig, Carpenter, Hamel, Randolph (bib0105) 2010; 99
Maa, Hsu (bib0060) 1997; 54
Brook (bib0165) 2000
Brook (bib0175) 2000
Banga, Mitra (bib0130) 1993; 1
Pereira, Bishai (bib0010) 2010; 9
Lankers, Munhall, Valet (bib0055) 2008; 14
Li, Pinnamaneni, Quan, Jaiswal, Andersson, Zhang (bib0145) 2012; 29
Esfandiary, Joshi, Vilivalam, Middaugh (bib0070) 2008
18636406 - Biotechnol Bioeng. 1997 Jun 20;54(6):503-12
15736189 - J Pharm Sci. 2005 Apr;94(4):918-27
3542458 - Diabetes Care. 1986 Nov-Dec;9(6):672-3
9141131 - Proteins. 1997 Apr;27(4):507-16
19534559 - J Phys Chem B. 2009 Jun 25;113(25):8453-7
17496011 - Biophys J. 2007 Sep 15;93(6):2143-51
9631292 - Curr Opin Struct Biol. 1998 Apr;8(2):189-94
19894257 - J Pharm Sci. 2010 Apr;99(4):1721-33
25256796 - J Pharm Sci. 2015 Feb;104(2):527-35
15124199 - J Pharm Sci. 2004 Jun;93(6):1390-402
19821758 - Diabetes Technol Ther. 2009 Oct;11(10):657-61
1946348 - Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9377-81
16378411 - Langmuir. 2006 Jan 3;22(1):134-9
23023774 - J Pharm Sci. 2012 Dec;101(12):4569-83
8069577 - J Drug Target. 1993;1(4):341-5
23280943 - J Pharm Sci. 2013 Mar;102(3):852-65
19360857 - J Pharm Sci. 2009 Sep;98(9):3167-81
2079389 - Int J Pept Protein Res. 1990 Oct;36(4):344-9
3322733 - Diabetes Care. 1987 Nov-Dec;10(6):786-7
21087111 - Expert Rev Vaccines. 2010 Nov;9(11):1343-9
9613806 - Biomaterials. 1997 Dec;18(24):1593-7
18627199 - Biomacromolecules. 2008 Aug;9(8):2153-61
18601196 - Biotechnol Bioeng. 1992 Oct 20;40(8):895-903
8110743 - Biochemistry. 1994 Feb 8;33(5):1116-24
20399286 - Biochim Biophys Acta. 2010 Jul;1804(7):1405-12
25800359 - Colloids Surf B Biointerfaces. 2015 Apr 1;128:586-93
11785697 - Pharm Res. 2001 Dec;18(12 ):1754-9
19864624 - Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):18990-5
21146492 - Anal Biochem. 2011 Mar 15;410(2):191-9
22350802 - Pharm Res. 2012 Jun;29(6):1689-97
11352739 - Biochemistry. 2001 May 22;40(20):6036-46
Zelisko (10.1016/j.heliyon.2017.e00264_bib0090) 2002; 18
Felsovalyi (10.1016/j.heliyon.2017.e00264_bib0050) 2012; 101
Sluzky (10.1016/j.heliyon.2017.e00264_bib0155) 1991; 88
Ludwig (10.1016/j.heliyon.2017.e00264_bib0105) 2010; 99
Ivanova (10.1016/j.heliyon.2017.e00264_bib0200) 2009; 106
Brook (10.1016/j.heliyon.2017.e00264_bib0175) 2000
Carré (10.1016/j.heliyon.2017.e00264_bib0030) 2006; 22
Brook (10.1016/j.heliyon.2017.e00264_bib0165) 2000
Pereira (10.1016/j.heliyon.2017.e00264_bib0010) 2010; 9
Bernstein (10.1016/j.heliyon.2017.e00264_bib0115) 1987; 10
Kwon (10.1016/j.heliyon.2017.e00264_bib0195) 2001; 18
Amiji (10.1016/j.heliyon.2017.e00264_bib0205) 1995; 21
Asakura (10.1016/j.heliyon.2017.e00264_bib0005) 2009; 11
Dodson (10.1016/j.heliyon.2017.e00264_bib0185) 1998; 8
Jones (10.1016/j.heliyon.2017.e00264_bib0150) 2005; 94
Dathe (10.1016/j.heliyon.2017.e00264_bib0125) 1990; 36
Nayef (10.1016/j.heliyon.2017.e00264_bib0170) 2015; 128
Smith (10.1016/j.heliyon.2017.e00264_bib0210) 2007; 93
Rapra (10.1016/j.heliyon.2017.e00264_bib0020) 2015
Basu (10.1016/j.heliyon.2017.e00264_bib0065) 2013; 102
Lankers (10.1016/j.heliyon.2017.e00264_bib0055) 2008; 14
Biancalana (10.1016/j.heliyon.2017.e00264_bib0190) 2010; 1804
van der Linden (10.1016/j.heliyon.2017.e00264_bib0075) 2007; 12
Maa (10.1016/j.heliyon.2017.e00264_bib0060) 1997; 54
Ludwig (10.1016/j.heliyon.2017.e00264_bib0110) 2011; 410
Krayukhina (10.1016/j.heliyon.2017.e00264_bib0120) 2015; 104
Sluzky (10.1016/j.heliyon.2017.e00264_bib0160) 1992; 40
Zelisko (10.1016/j.heliyon.2017.e00264_bib0180) 2008; 9
Chantelau (10.1016/j.heliyon.2017.e00264_bib0215) 1986; 9
Millican (10.1016/j.heliyon.2017.e00264_bib0100) 1994; 33
Bekard (10.1016/j.heliyon.2017.e00264_bib0140) 2009; 113
Li (10.1016/j.heliyon.2017.e00264_bib0145) 2012; 29
Esfandiary (10.1016/j.heliyon.2017.e00264_bib0070) 2008
Thirumangalathu (10.1016/j.heliyon.2017.e00264_bib0080) 2009; 98
Woehl (10.1016/j.heliyon.2017.e00264_bib0040) 2003; 3
Banga (10.1016/j.heliyon.2017.e00264_bib0130) 1993; 1
Nielsen (10.1016/j.heliyon.2017.e00264_bib0135) 2001; 40
Shire (10.1016/j.heliyon.2017.e00264_bib0015) 2004; 93
Sun (10.1016/j.heliyon.2017.e00264_bib0085) 1997; 18
Brange (10.1016/j.heliyon.2017.e00264_bib0095) 1997; 27
Noll (10.1016/j.heliyon.2017.e00264_bib0035) 1968
Kasi (10.1016/j.heliyon.2017.e00264_bib0025) 2013; 5
(10.1016/j.heliyon.2017.e00264_bib0045) 2013
References_xml – volume: 3
  start-page: 427
  year: 2003
  end-page: 439
  ident: bib0040
  article-title: Viscous dissipation and rheological behavior near the solid/liquid/vapor triple line, Application to the spreading of silicone oils
  publication-title: Contact Angle, Wettability and Adhesion
  contributor:
    fullname: Carre
– volume: 5
  start-page: 181
  year: 2013
  end-page: 186
  ident: bib0025
  article-title: Prefilled syringes versus vials: Impact on vaccination efficiency and patient safety in Indian private market
  publication-title: Pediatr. Infect. Dis.
  contributor:
    fullname: Mitra
– volume: 98
  start-page: 3167
  year: 2009
  end-page: 3181
  ident: bib0080
  article-title: Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Carpenter
– volume: 9
  start-page: 1343
  year: 2010
  end-page: 1349
  ident: bib0010
  article-title: Vaccine presentation in the USA: economics of prefilled syringes versus multidose vials for influenza vaccination
  publication-title: Expert Rev. Vaccines
  contributor:
    fullname: Bishai
– volume: 102
  start-page: 852
  year: 2013
  end-page: 865
  ident: bib0065
  article-title: IgG1 aggregation and particle formation induced by silicone‐water interfaces on siliconized borosilicate glass beads: A model for siliconized primary containers
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Carpenter
– volume: 8
  start-page: 189
  year: 1998
  end-page: 194
  ident: bib0185
  article-title: The role of assembly in insulin's biosynthesis
  publication-title: Curr. Opin. Struct. Biol.
  contributor:
    fullname: Steiner
– volume: 14
  start-page: 1612
  year: 2008
  end-page: 1613
  ident: bib0055
  article-title: Differentiation between foreign particulate matter and silicone oil induced protein aggregation in drug solutions by automated raman spectroscopy
  publication-title: Microsp. Microanal.
  contributor:
    fullname: Valet
– volume: 18
  start-page: 1754
  year: 2001
  end-page: 1759
  ident: bib0195
  article-title: In situ study of insulin aggregation induced by water-organic solvent interface
  publication-title: Pharm. Res.
  contributor:
    fullname: Kim
– volume: 29
  start-page: 1689
  year: 2012
  end-page: 1697
  ident: bib0145
  article-title: Mechanistic understanding of protein-silicone oil interactions
  publication-title: Pharm. Res.
  contributor:
    fullname: Zhang
– volume: 10
  start-page: 786
  year: 1987
  end-page: 787
  ident: bib0115
  article-title: Clouding and Deactivation of Clear (Regular) Human Insulin: Association With Silicone Oil From Disposable Syringes?
  publication-title: Diabetes Care
  contributor:
    fullname: Bernstein
– volume: 101
  start-page: 4569
  year: 2012
  end-page: 4583
  ident: bib0050
  article-title: Silicone-oil-based subvisible particles: Their detection, interactions, and regulation in prefilled container closure systems for biopharmaceuticals
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Mangiagalli
– volume: 33
  start-page: 1116
  year: 1994
  end-page: 1124
  ident: bib0100
  article-title: Equilibrium Intermediates in the Denaturation of Human Insulin and Two Monomeric Insulin Analogs
  publication-title: Biochem.
  contributor:
    fullname: Brems
– volume: 410
  start-page: 191
  year: 2011
  end-page: 199
  ident: bib0110
  article-title: Flow cytometry: A promising technique for the study of silicone oil-induced particulate formation in protein formulations
  publication-title: Anal. Biochem.
  contributor:
    fullname: Randolph
– volume: 99
  start-page: 1721
  year: 2010
  end-page: 1733
  ident: bib0105
  article-title: Protein Adsorption and Excipient Effects on Kinetic Stability of Silicone Oil Emulsions
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Randolph
– start-page: 22
  year: 2008
  end-page: 25
  ident: bib0070
  publication-title: Characterization of protein aggregation and adsorption on prefillable syringe surfaces
  contributor:
    fullname: Middaugh
– volume: 1804
  start-page: 1405
  year: 2010
  end-page: 1412
  ident: bib0190
  article-title: Molecular mechanism of Thioflavin-T binding to amyloid fibrils
  publication-title: Biochim. Biophys. Acta (BBA)-Proteins and Proteomics
  contributor:
    fullname: Koide
– volume: 40
  start-page: 895
  year: 1992
  end-page: 903
  ident: bib0160
  article-title: Mechanism of insulin aggregation and stabilization in agitated aqueous solutions
  publication-title: Biotechnol. Bioeng.
  contributor:
    fullname: Langer
– volume: 9
  start-page: 2153
  year: 2008
  end-page: 2161
  ident: bib0180
  article-title: Water-in-Silicone Oil Emulsion Stabilizing Surfactants Formed From Native Albumin and Triethoxysilylpropyl-Polydimethylsiloxane
  publication-title: Biomacromolecules
  contributor:
    fullname: Brook
– volume: 18
  start-page: 1593
  year: 1997
  end-page: 1597
  ident: bib0085
  article-title: Protein denaturation induced by cyclic silicone
  publication-title: Biomaterials
  contributor:
    fullname: Chen
– volume: 27
  start-page: 507
  year: 1997
  end-page: 516
  ident: bib0095
  article-title: A model of insulin fibrils derived from the X‐ray crystal structure of a monomeric insulin (despentapeptide insulin)
  publication-title: Proteins: Struct., Funct. Bioinf.
  contributor:
    fullname: Whittingham
– year: 2015
  ident: bib0020
  article-title: The Future of Alliances and Partnerships in the Pre-Filled Syringes Market to 2020
  contributor:
    fullname: Rapra
– volume: 104
  start-page: 527
  year: 2015
  end-page: 535
  ident: bib0120
  article-title: Effects of Syringe Material and Silicone Oil Lubrication on the Stability of Pharmaceutical Proteins
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Fukui
– volume: 94
  start-page: 918
  year: 2005
  end-page: 927
  ident: bib0150
  article-title: Silicone oil induced aggregation of proteins
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Middaugh
– volume: 12
  start-page: 158
  year: 2007
  end-page: 165
  ident: bib0075
  article-title: Self-assembly and aggregation of proteins
  publication-title: Curr. Opin. Colloid Interface Sci.
  contributor:
    fullname: Venema
– volume: 36
  start-page: 344
  year: 1990
  end-page: 349
  ident: bib0125
  article-title: Insulin aggregation in solution
  publication-title: Int. J. Peptide Protein Res.
  contributor:
    fullname: Mehlis
– volume: 40
  start-page: 6036
  year: 2001
  end-page: 6046
  ident: bib0135
  article-title: Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism
  publication-title: Biochem.
  contributor:
    fullname: Fink
– year: 2013
  ident: bib0045
  article-title: Silicone fluids: property profile guide
– volume: 22
  start-page: 134
  year: 2006
  end-page: 139
  ident: bib0030
  article-title: Spreading of Silicone Oils on Glass in Two Geometries
  publication-title: Langmuir
  contributor:
    fullname: Woehl
– volume: 1
  start-page: 341
  year: 1993
  end-page: 345
  ident: bib0130
  article-title: Minimization of shaking-induced formation of insoluble aggregates of insulin by cyclodextrins
  publication-title: J. Drug Target.
  contributor:
    fullname: Mitra
– volume: 93
  start-page: 2143
  year: 2007
  end-page: 2151
  ident: bib0210
  article-title: Nucleation and growth of insulin fibrils in bulk solution and at hydrophobic polystyrene surfaces
  publication-title: Biophys. J.
  contributor:
    fullname: Roberts
– volume: 21
  start-page: 1661
  year: 1995
  end-page: 1669
  ident: bib0205
  article-title: Photophysical Characterization of Insulin Denaturation and Aggregation at Hydrophobic Interfaces
  publication-title: Drug Devel. Ind. Pharm.
  contributor:
    fullname: Boroujerdi
– volume: 113
  start-page: 8453
  year: 2009
  end-page: 8457
  ident: bib0140
  article-title: Shear-induced deformation of bovine insulin in Couette flow
  publication-title: J. Phys. Chem. B
  contributor:
    fullname: Dunstan
– start-page: 256
  year: 2000
  end-page: 308
  ident: bib0165
  article-title: Silicones: Silicon in Organic, Organometallic and Polymer Chemistry
  contributor:
    fullname: Brook
– volume: 128
  start-page: 586
  year: 2015
  end-page: 593
  ident: bib0170
  article-title: Low molecular weight silicones particularly facilitate human serum albumin denaturation
  publication-title: Colloids. Surf. B
  contributor:
    fullname: Brook
– volume: 11
  start-page: 657
  year: 2009
  end-page: 661
  ident: bib0005
  article-title: A comparison of the handling and accuracy of syringe and vial versus prefilled insulin pen (FlexPen)
  publication-title: Diabetes Technol. Ther.
  contributor:
    fullname: Yohkoh
– volume: 93
  start-page: 1390
  year: 2004
  end-page: 1402
  ident: bib0015
  article-title: Challenges in the development of high protein concentration formulations
  publication-title: J. Pharm. Sci.
  contributor:
    fullname: Liu
– volume: 88
  start-page: 9377
  year: 1991
  end-page: 9381
  ident: bib0155
  article-title: Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces
  publication-title: PNAS
  contributor:
    fullname: Langer
– volume: 18
  start-page: 8982
  year: 2002
  end-page: 8987
  ident: bib0090
  article-title: Stabilization of alpha-chymotrypsin and lysozyme entrapped water-in-silicone oil emulsions
  publication-title: Langmuir
  contributor:
    fullname: Brook
– volume: 9
  start-page: 672
  year: 1986
  end-page: 673
  ident: bib0215
  article-title: Silicone oil released from disposable insulin syringes
  publication-title: Diabetes Care
  contributor:
    fullname: Böhlken
– year: 1968
  ident: bib0035
  article-title: Chemistry and Technology of Silicones
  contributor:
    fullname: Noll
– volume: 106
  start-page: 18990
  year: 2009
  end-page: 18995
  ident: bib0200
  article-title: Molecular basis for insulin fibril assembly
  publication-title: PNAS
  contributor:
    fullname: Eisenberg
– year: 2000
  ident: bib0175
  article-title: Silicon in Organic, Organometallic, and Polymer Chemistry
  contributor:
    fullname: Brook
– volume: 54
  start-page: 503
  year: 1997
  end-page: 512
  ident: bib0060
  article-title: Protein denaturation by combined effect of shear and air-liquid interface
  publication-title: Biotechnol. Bioeng.
  contributor:
    fullname: Hsu
– start-page: 22
  year: 2008
  ident: 10.1016/j.heliyon.2017.e00264_bib0070
  contributor:
    fullname: Esfandiary
– volume: 99
  start-page: 1721
  issue: 4
  year: 2010
  ident: 10.1016/j.heliyon.2017.e00264_bib0105
  article-title: Protein Adsorption and Excipient Effects on Kinetic Stability of Silicone Oil Emulsions
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.21982
  contributor:
    fullname: Ludwig
– volume: 9
  start-page: 2153
  issue: 8
  year: 2008
  ident: 10.1016/j.heliyon.2017.e00264_bib0180
  article-title: Water-in-Silicone Oil Emulsion Stabilizing Surfactants Formed From Native Albumin and Triethoxysilylpropyl-Polydimethylsiloxane
  publication-title: Biomacromolecules
  doi: 10.1021/bm800226z
  contributor:
    fullname: Zelisko
– volume: 10
  start-page: 786
  issue: 6
  year: 1987
  ident: 10.1016/j.heliyon.2017.e00264_bib0115
  article-title: Clouding and Deactivation of Clear (Regular) Human Insulin: Association With Silicone Oil From Disposable Syringes?
  publication-title: Diabetes Care
  doi: 10.2337/diacare.10.6.786
  contributor:
    fullname: Bernstein
– volume: 104
  start-page: 527
  issue: 2
  year: 2015
  ident: 10.1016/j.heliyon.2017.e00264_bib0120
  article-title: Effects of Syringe Material and Silicone Oil Lubrication on the Stability of Pharmaceutical Proteins
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.24184
  contributor:
    fullname: Krayukhina
– volume: 102
  start-page: 852
  issue: 3
  year: 2013
  ident: 10.1016/j.heliyon.2017.e00264_bib0065
  article-title: IgG1 aggregation and particle formation induced by silicone‐water interfaces on siliconized borosilicate glass beads: A model for siliconized primary containers
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.23434
  contributor:
    fullname: Basu
– volume: 106
  start-page: 18990
  issue: 45
  year: 2009
  ident: 10.1016/j.heliyon.2017.e00264_bib0200
  article-title: Molecular basis for insulin fibril assembly
  publication-title: PNAS
  doi: 10.1073/pnas.0910080106
  contributor:
    fullname: Ivanova
– volume: 101
  start-page: 4569
  issue: 12
  year: 2012
  ident: 10.1016/j.heliyon.2017.e00264_bib0050
  article-title: Silicone-oil-based subvisible particles: Their detection, interactions, and regulation in prefilled container closure systems for biopharmaceuticals
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.23328
  contributor:
    fullname: Felsovalyi
– start-page: 256
  year: 2000
  ident: 10.1016/j.heliyon.2017.e00264_bib0165
  contributor:
    fullname: Brook
– volume: 14
  start-page: 1612
  issue: Supplement S2
  year: 2008
  ident: 10.1016/j.heliyon.2017.e00264_bib0055
  article-title: Differentiation between foreign particulate matter and silicone oil induced protein aggregation in drug solutions by automated raman spectroscopy
  publication-title: Microsp. Microanal.
  doi: 10.1017/S1431927608086807
  contributor:
    fullname: Lankers
– year: 1968
  ident: 10.1016/j.heliyon.2017.e00264_bib0035
  contributor:
    fullname: Noll
– volume: 18
  start-page: 8982
  issue: 23
  year: 2002
  ident: 10.1016/j.heliyon.2017.e00264_bib0090
  article-title: Stabilization of alpha-chymotrypsin and lysozyme entrapped water-in-silicone oil emulsions
  publication-title: Langmuir
  doi: 10.1021/la025867k
  contributor:
    fullname: Zelisko
– volume: 88
  start-page: 9377
  year: 1991
  ident: 10.1016/j.heliyon.2017.e00264_bib0155
  article-title: Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces
  publication-title: PNAS
  doi: 10.1073/pnas.88.21.9377
  contributor:
    fullname: Sluzky
– year: 2015
  ident: 10.1016/j.heliyon.2017.e00264_bib0020
  contributor:
    fullname: Rapra
– volume: 21
  start-page: 1661
  year: 1995
  ident: 10.1016/j.heliyon.2017.e00264_bib0205
  article-title: Photophysical Characterization of Insulin Denaturation and Aggregation at Hydrophobic Interfaces
  publication-title: Drug Devel. Ind. Pharm.
  doi: 10.3109/03639049509069255
  contributor:
    fullname: Amiji
– volume: 36
  start-page: 344
  issue: 4
  year: 1990
  ident: 10.1016/j.heliyon.2017.e00264_bib0125
  article-title: Insulin aggregation in solution
  publication-title: Int. J. Peptide Protein Res.
  doi: 10.1111/j.1399-3011.1990.tb01292.x
  contributor:
    fullname: Dathe
– year: 2000
  ident: 10.1016/j.heliyon.2017.e00264_bib0175
  contributor:
    fullname: Brook
– volume: 1804
  start-page: 1405
  issue: 7
  year: 2010
  ident: 10.1016/j.heliyon.2017.e00264_bib0190
  article-title: Molecular mechanism of Thioflavin-T binding to amyloid fibrils
  publication-title: Biochim. Biophys. Acta (BBA)-Proteins and Proteomics
  doi: 10.1016/j.bbapap.2010.04.001
  contributor:
    fullname: Biancalana
– volume: 40
  start-page: 895
  issue: 8
  year: 1992
  ident: 10.1016/j.heliyon.2017.e00264_bib0160
  article-title: Mechanism of insulin aggregation and stabilization in agitated aqueous solutions
  publication-title: Biotechnol. Bioeng.
  doi: 10.1002/bit.260400805
  contributor:
    fullname: Sluzky
– volume: 3
  start-page: 427
  year: 2003
  ident: 10.1016/j.heliyon.2017.e00264_bib0040
  article-title: Viscous dissipation and rheological behavior near the solid/liquid/vapor triple line, Application to the spreading of silicone oils
  contributor:
    fullname: Woehl
– volume: 22
  start-page: 134
  issue: 1
  year: 2006
  ident: 10.1016/j.heliyon.2017.e00264_bib0030
  article-title: Spreading of Silicone Oils on Glass in Two Geometries
  publication-title: Langmuir
  doi: 10.1021/la0518997
  contributor:
    fullname: Carré
– year: 2013
  ident: 10.1016/j.heliyon.2017.e00264_bib0045
– volume: 8
  start-page: 189
  issue: 2
  year: 1998
  ident: 10.1016/j.heliyon.2017.e00264_bib0185
  article-title: The role of assembly in insulin's biosynthesis
  publication-title: Curr. Opin. Struct. Biol.
  doi: 10.1016/S0959-440X(98)80037-7
  contributor:
    fullname: Dodson
– volume: 93
  start-page: 2143
  issue: 6
  year: 2007
  ident: 10.1016/j.heliyon.2017.e00264_bib0210
  article-title: Nucleation and growth of insulin fibrils in bulk solution and at hydrophobic polystyrene surfaces
  publication-title: Biophys. J.
  doi: 10.1529/biophysj.107.105338
  contributor:
    fullname: Smith
– volume: 9
  start-page: 672
  issue: 6
  year: 1986
  ident: 10.1016/j.heliyon.2017.e00264_bib0215
  article-title: Silicone oil released from disposable insulin syringes
  publication-title: Diabetes Care
  doi: 10.2337/diacare.9.6.672
  contributor:
    fullname: Chantelau
– volume: 113
  start-page: 8453
  issue: 25
  year: 2009
  ident: 10.1016/j.heliyon.2017.e00264_bib0140
  article-title: Shear-induced deformation of bovine insulin in Couette flow
  publication-title: J. Phys. Chem. B
  doi: 10.1021/jp903522e
  contributor:
    fullname: Bekard
– volume: 410
  start-page: 191
  issue: 2
  year: 2011
  ident: 10.1016/j.heliyon.2017.e00264_bib0110
  article-title: Flow cytometry: A promising technique for the study of silicone oil-induced particulate formation in protein formulations
  publication-title: Anal. Biochem.
  doi: 10.1016/j.ab.2010.12.008
  contributor:
    fullname: Ludwig
– volume: 11
  start-page: 657
  issue: 10
  year: 2009
  ident: 10.1016/j.heliyon.2017.e00264_bib0005
  article-title: A comparison of the handling and accuracy of syringe and vial versus prefilled insulin pen (FlexPen)
  publication-title: Diabetes Technol. Ther.
  doi: 10.1089/dia.2009.0006
  contributor:
    fullname: Asakura
– volume: 94
  start-page: 918
  issue: 4
  year: 2005
  ident: 10.1016/j.heliyon.2017.e00264_bib0150
  article-title: Silicone oil induced aggregation of proteins
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.20321
  contributor:
    fullname: Jones
– volume: 27
  start-page: 507
  issue: 4
  year: 1997
  ident: 10.1016/j.heliyon.2017.e00264_bib0095
  article-title: A model of insulin fibrils derived from the X‐ray crystal structure of a monomeric insulin (despentapeptide insulin)
  publication-title: Proteins: Struct., Funct. Bioinf.
  doi: 10.1002/(SICI)1097-0134(199704)27:4<507::AID-PROT4>3.0.CO;2-7
  contributor:
    fullname: Brange
– volume: 18
  start-page: 1754
  issue: 12
  year: 2001
  ident: 10.1016/j.heliyon.2017.e00264_bib0195
  article-title: In situ study of insulin aggregation induced by water-organic solvent interface
  publication-title: Pharm. Res.
  doi: 10.1023/A:1013334916162
  contributor:
    fullname: Kwon
– volume: 5
  start-page: 181
  issue: 4
  year: 2013
  ident: 10.1016/j.heliyon.2017.e00264_bib0025
  article-title: Prefilled syringes versus vials: Impact on vaccination efficiency and patient safety in Indian private market
  publication-title: Pediatr. Infect. Dis.
  doi: 10.1016/j.pid.2013.11.005
  contributor:
    fullname: Kasi
– volume: 54
  start-page: 503
  issue: 6
  year: 1997
  ident: 10.1016/j.heliyon.2017.e00264_bib0060
  article-title: Protein denaturation by combined effect of shear and air-liquid interface
  publication-title: Biotechnol. Bioeng.
  doi: 10.1002/(SICI)1097-0290(19970620)54:6<503::AID-BIT1>3.0.CO;2-N
  contributor:
    fullname: Maa
– volume: 18
  start-page: 1593
  issue: 24
  year: 1997
  ident: 10.1016/j.heliyon.2017.e00264_bib0085
  article-title: Protein denaturation induced by cyclic silicone
  publication-title: Biomaterials
  doi: 10.1016/S0142-9612(97)00105-1
  contributor:
    fullname: Sun
– volume: 1
  start-page: 341
  issue: 4
  year: 1993
  ident: 10.1016/j.heliyon.2017.e00264_bib0130
  article-title: Minimization of shaking-induced formation of insoluble aggregates of insulin by cyclodextrins
  publication-title: J. Drug Target.
  doi: 10.3109/10611869308996093
  contributor:
    fullname: Banga
– volume: 29
  start-page: 1689
  issue: 6
  year: 2012
  ident: 10.1016/j.heliyon.2017.e00264_bib0145
  article-title: Mechanistic understanding of protein-silicone oil interactions
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-012-0696-6
  contributor:
    fullname: Li
– volume: 93
  start-page: 1390
  issue: 6
  year: 2004
  ident: 10.1016/j.heliyon.2017.e00264_bib0015
  article-title: Challenges in the development of high protein concentration formulations
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.20079
  contributor:
    fullname: Shire
– volume: 128
  start-page: 586
  issue: 0
  year: 2015
  ident: 10.1016/j.heliyon.2017.e00264_bib0170
  article-title: Low molecular weight silicones particularly facilitate human serum albumin denaturation
  publication-title: Colloids. Surf. B
  doi: 10.1016/j.colsurfb.2015.03.013
  contributor:
    fullname: Nayef
– volume: 98
  start-page: 3167
  issue: 9
  year: 2009
  ident: 10.1016/j.heliyon.2017.e00264_bib0080
  article-title: Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.21719
  contributor:
    fullname: Thirumangalathu
– volume: 12
  start-page: 158
  issue: 4-5
  year: 2007
  ident: 10.1016/j.heliyon.2017.e00264_bib0075
  article-title: Self-assembly and aggregation of proteins
  publication-title: Curr. Opin. Colloid Interface Sci.
  doi: 10.1016/j.cocis.2007.07.010
  contributor:
    fullname: van der Linden
– volume: 33
  start-page: 1116
  issue: 5
  year: 1994
  ident: 10.1016/j.heliyon.2017.e00264_bib0100
  article-title: Equilibrium Intermediates in the Denaturation of Human Insulin and Two Monomeric Insulin Analogs
  publication-title: Biochem.
  doi: 10.1021/bi00171a010
  contributor:
    fullname: Millican
– volume: 40
  start-page: 6036
  issue: 20
  year: 2001
  ident: 10.1016/j.heliyon.2017.e00264_bib0135
  article-title: Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism
  publication-title: Biochem.
  doi: 10.1021/bi002555c
  contributor:
    fullname: Nielsen
– volume: 9
  start-page: 1343
  issue: 11
  year: 2010
  ident: 10.1016/j.heliyon.2017.e00264_bib0010
  article-title: Vaccine presentation in the USA: economics of prefilled syringes versus multidose vials for influenza vaccination
  publication-title: Expert Rev. Vaccines
  doi: 10.1586/erv.10.129
  contributor:
    fullname: Pereira
SSID ssj0001586973
Score 2.12904
Snippet Protein drugs such as insulin are almost universally delivered via glass syringes lubricated with silicone oil. It is not uncommon for prefilled syringes (PFS)...
SourceID doaj
pubmedcentral
proquest
crossref
pubmed
elsevier
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage e00264
SubjectTerms Biochemistry
Bioengineering
Biotechnology
Inorganic chemistry
Organic chemistry
SummonAdditionalLinks – databaseName: Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEBYhh5JLSd9O0qJCr96VY0mWjk1pCIX0lMDehGSNyIbtbtgHZaE_PiPJ3qzbQy4FH2zLSJZmpPlGmgchX6CpXN1UutR1qEveBlainiXKOrSglWXB2-jvfP1TXt3yHxMx2Uv1FW3CcnjgPHBj7cEr5c_BB-D6vHWtVagNctAauLc5EijTe8pU9g9WUqfjZZRYolScsyf3nfH96A5m0-0ixj-tmhFERYQPBFOK3z-QT__iz7_NKPfk0uUxedkBSvo1d-QVOYD5a_Liujsyf0P-ICNQhIDJCHZLF4F25ud0x3U0PmzTBh_e45U2GsBTt6UxE0YsobOYTo3-6rPp0t9pT5WusFpUqYHONi4tqesVtUug1kWvprfk9vL7zbersku5ULaI-9ZIIoSDOFgSPC5l3NZWOeYR48WJXTFAuMJF5bUPqOhIHbzEBVNxwazwUllRvyOHc2z0A6GaaVwvZIv6Y8OlDQ5AMcuVD8KJVjUFGfXjbR5yZA3Tm5zdm45AJhLIZAIV5CJSZfdxDIydXiC7mI5dzHPsUhDV09R0GCNjB6xq-lz7n3seMDgH48GKncNiszKVUrVCPU7LgrzPPLH7S4RvMqKygjQDbhl0Y1gyn96lON8CwQUCspP_0e9TchS7kq3nzsjhermBjwin1u5TmjmPrPsi2Q
  priority: 102
  providerName: Directory of Open Access Journals
Title The stability of insulin solutions in syringes is improved by ensuring lower molecular weight silicone lubricants are absent
URI https://dx.doi.org/10.1016/j.heliyon.2017.e00264
https://www.ncbi.nlm.nih.gov/pubmed/28367509
https://search.proquest.com/docview/1883842896
https://pubmed.ncbi.nlm.nih.gov/PMC5362151
https://doaj.org/article/9ded88d2edfe492cbca8eb24e99e4da4
Volume 3
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Li9swEBa7Wyi9lL432zao0KsdO5Zs6diGLksh2x66EHoReoy6WRJnyYMS2B_fkWyn6_ZQKOTgxImseD7NfCPPg5D3UOWmqHKZyMIXCbM-S9DP4knhLUihM-90yHeeXpYXV-zzjM-OCO9yYWLQvjXztF4s03p-HWMrb5d21MWJjb5OJxy1Llqq0TE5RoDec9Gb1GBRyqr4na0zukmvYTHfr0K507xKIfgdoR8PWtYyGMyeSYqV-3uW6W_m-WcA5T2LdP6EPG6pJP3QTPkpOYL6GXk4bR-WPyd3CAGK5C-Gv-7pytM28Jwe8EbDm33c2sNjfMUtBnDU7GnogRHO0EVopEaXXR9d-jPuptINDovONNDFzkRlut1QvQaqTchnekGuzj99m1wkbbOFxCLj26JwkAgyNO_gUIkxXWhhMofsLizpPAMkKoznTjqPLk4pvStRVQrGM81dKTQvXpKTGi96SqjMJGqK0qLnWLFSewMgMs2E89xwK6oBSbv7rW6bmhqqCza7Ua2sVJCVamQ1IB-DVA5fDiWx4wer9Q_VAkNJB04INwbngcmxNVYLMGMGUgJzGgcRnUxVyy4a1oBDzf91_XcdBhSuvvBIRdew2m1ULkQh0IOT5YC8ajBxmGUHrwGpemjp_Y3-GQR8rPDdAvzsv3_5mjwK82-C5d6Qk-16B2-RPW3NMO46DMmDy8nsy_dhXDu_AP6iIZM
link.rule.ids 230,315,730,783,787,867,888,2109,27936,27937,53804,53806
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Nb9MwFLfGkGAXvmHl00hckyaNndhHmJgKrBOHDe1m2fEz62jTqU2FivjjeXaSsowDAqmHNm6dWu_n937PeR-EvIEiNVmRykhmLotY6ZII_SweZa4EKXTirPb5zpPjfHzKPp7xsx3Cu1yYELRfmmlczeZxNT0PsZWX83LYxYkNP08OOGpdtFTDG-Qm7teEXXHSm-Rgkcsi-52vM7yIz2E23Sx8wdO0iMF7Hr4jD9rW3JvMnlEKtft7tulP7nk9hPKKTTq8S750q2lCUb7F69rE5Y9rhR7_ebn3yJ2WpdK3zfB9sgPVA3Jr0j6Hf0h-Iroo8soQWbuhC0fbmHa6hTL1Hzbh1BDf4yucXoClZkN9ew0_Qme-Rxuddy166fdwUEtXOC366UBnaxP0dL2ieglUG58q9YicHr4_ORhHbR-HqEQyWaPckWMyZA5gUT8ynWlhEovE0WuLNAHkQIynVlqH3lMunc1RqoLxRHObC82zx2S3wpvuEyoTiUooL9EpLViunQEQiWbCOm54KYoBiTtBqsumXIfq4tguVAsC5UGgGhAMyDsv7u2XfbXtcGGx_KpaIShpwQphR2AdMDkqTakFmBEDKYFZjZOIDiyqJS4NIcGppn-7_-sOXAo3tn9aoytYrFcqFSIT6BzKfECeNGDb_ssOtwNS9GDYW0Z_BMEVioe3YHr63798RW6PTyZH6ujD8adnZM-vpYnJe0526-UaXiBJq83LsCV_AajpQNY
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9NAEF5BkSoulDcpr0Xi6le8Xu8eoRCVR6oeqFRxWe2zTUmcKHGEgvjxzK7tEJcDUiUf_Fx7Nd_OfLOenUHorS0zlZcZj3ju8ohol0bgZxVR7rTlTKbOSL_eeXxCj8_I5_PifKfUVwja12oSV9NZXE0uQ2zlYqaTLk4sOR0fFaB1wVIlC-OS2-gOjNmU7jjqzQJhRnmZ_12zk1zFl3Y62cx90tOsjK33PnxVHrCv1JvNnmEK-ft79ulf_nk9jHLHLo0O0PeuR004yo94XatY_7qW7PFGXb6P7rVsFb9rbnmAbtnqIdoft__jH6HfgDIM_DJE2G7w3OE2th1vIY39wSbMHsI-bGEWwxqsNtiX2fBX8NTXasOzrlQv_hkmbPEKmgV_3eLpWgV9Xa-wXFoslV8y9RidjT5-OzqO2noOkQZSWYP8gWsSYBDWgJ4kMpdMpQYIpNcaWWqBC5EiM9w48KIod4aCZBkpUlkYymSRP0F7Fbz0GcI85aCMqAbntCRUOmUtSyVhxhWq0KwcoLgTplg0aTtEF892JVogCA8E0QBhgN57kW9v9lm3w4n58kK0ghDcWMOYGVrjLOFDrbRkVg2J5dwSI6ER1gFGtASmISbQ1OR_73_TAUzAAPd_bWRl5-uVyBjLGTiJnA7Q0wZw26_ssDtAZQ-KvW70rwDAQhLxFlCHN37yNdo__TASXz-dfHmO7vquNKF5L9BevVzbl8DVavUqjMo_fQtDVg
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+stability+of+insulin+solutions+in+syringes+is+improved+by+ensuring+lower+molecular+weight+silicone+lubricants+are+absent&rft.jtitle=Heliyon&rft.au=Nayef%2C+Lamees&rft.au=Khan%2C+Madiha+F&rft.au=Brook%2C+Michael+A&rft.date=2017-03-01&rft.issn=2405-8440&rft.eissn=2405-8440&rft.volume=3&rft.issue=3&rft.spage=e00264&rft.epage=e00264&rft_id=info:doi/10.1016%2Fj.heliyon.2017.e00264&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2405-8440&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2405-8440&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2405-8440&client=summon