High Throughput Protein Formulation Platform: Case Study of Salmon Calcitonin

Purpose The feasibility of using high throughput spectroscopy for characterization and selection of physically stable protein formulations was studied. Materials and Methods A hundred aqueous formulations of salmon calcitonin (sCT) were prepared using 20 buffer compositions. The solutions had pH val...

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Veröffentlicht in:Pharmaceutical research 2009-01, Vol.26 (1), p.118-128
Hauptverfasser: Capelle, Martinus A. H, Gurny, Robert, Arvinte, Tudor
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Gurny, Robert
Arvinte, Tudor
description Purpose The feasibility of using high throughput spectroscopy for characterization and selection of physically stable protein formulations was studied. Materials and Methods A hundred aqueous formulations of salmon calcitonin (sCT) were prepared using 20 buffer compositions. The solutions had pH values between 2.5 and 10.5. The stability of the sCT formulations was analyzed over 1 week by the following assays: (1) protein concentration, (2) volume control by measuring pathlength, (3) turbidity (absorbance at 350 nm), (4) intrinsic tyrosine fluorescence, (5) 1-anilino-naphthalene-8-sulfonate (ANS) fluorescence, (6) Nile Red fluorescence. Addition of the dyes (Nile Red and ANS) was used to study protein conformational changes. Results After 1 day, 27 out of the 100 formulations of salmon calcitonin were stable. After 7 days, 12 stable sCT formulations remained. The best salmon calcitonin formulation was in 10 mM sodium acetate buffer with pH values between 3.5 and 5.5. Conclusions The findings are in accordance with the sCT formulations that were patented and used commercially. This can be considered as a proof of concept for the high throughput protein formulation platform.
doi_str_mv 10.1007/s11095-008-9662-8
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H ; Gurny, Robert ; Arvinte, Tudor</creator><creatorcontrib>Capelle, Martinus A. H ; Gurny, Robert ; Arvinte, Tudor</creatorcontrib><description>Purpose The feasibility of using high throughput spectroscopy for characterization and selection of physically stable protein formulations was studied. Materials and Methods A hundred aqueous formulations of salmon calcitonin (sCT) were prepared using 20 buffer compositions. The solutions had pH values between 2.5 and 10.5. The stability of the sCT formulations was analyzed over 1 week by the following assays: (1) protein concentration, (2) volume control by measuring pathlength, (3) turbidity (absorbance at 350 nm), (4) intrinsic tyrosine fluorescence, (5) 1-anilino-naphthalene-8-sulfonate (ANS) fluorescence, (6) Nile Red fluorescence. Addition of the dyes (Nile Red and ANS) was used to study protein conformational changes. Results After 1 day, 27 out of the 100 formulations of salmon calcitonin were stable. After 7 days, 12 stable sCT formulations remained. The best salmon calcitonin formulation was in 10 mM sodium acetate buffer with pH values between 3.5 and 5.5. Conclusions The findings are in accordance with the sCT formulations that were patented and used commercially. This can be considered as a proof of concept for the high throughput protein formulation platform.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-008-9662-8</identifier><identifier>PMID: 18600433</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>Boston: Boston : Springer US</publisher><subject>Anilino Naphthalenesulfonates - chemistry ; Biochemistry ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Bone Density Conservation Agents - administration &amp; dosage ; Bone Density Conservation Agents - chemistry ; Buffers ; Calcitonin - administration &amp; dosage ; Calcitonin - chemistry ; Chemistry, Pharmaceutical ; Drug Evaluation, Preclinical - methods ; Feasibility studies ; Fluorescent Dyes ; General pharmacology ; high throughput screening ; Hydrogen-Ion Concentration ; Medical Law ; Medical sciences ; Oxazines ; Pharmaceutical sciences ; Pharmaceutical Solutions ; Pharmaceutical technology. 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H</creatorcontrib><creatorcontrib>Gurny, Robert</creatorcontrib><creatorcontrib>Arvinte, Tudor</creatorcontrib><title>High Throughput Protein Formulation Platform: Case Study of Salmon Calcitonin</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose The feasibility of using high throughput spectroscopy for characterization and selection of physically stable protein formulations was studied. Materials and Methods A hundred aqueous formulations of salmon calcitonin (sCT) were prepared using 20 buffer compositions. The solutions had pH values between 2.5 and 10.5. The stability of the sCT formulations was analyzed over 1 week by the following assays: (1) protein concentration, (2) volume control by measuring pathlength, (3) turbidity (absorbance at 350 nm), (4) intrinsic tyrosine fluorescence, (5) 1-anilino-naphthalene-8-sulfonate (ANS) fluorescence, (6) Nile Red fluorescence. Addition of the dyes (Nile Red and ANS) was used to study protein conformational changes. Results After 1 day, 27 out of the 100 formulations of salmon calcitonin were stable. After 7 days, 12 stable sCT formulations remained. The best salmon calcitonin formulation was in 10 mM sodium acetate buffer with pH values between 3.5 and 5.5. Conclusions The findings are in accordance with the sCT formulations that were patented and used commercially. 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Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>protein formulation</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>Salmon</topic><topic>salmon calcitonin</topic><topic>Spectrometry, Fluorescence</topic><topic>Spectrophotometry, Ultraviolet</topic><topic>spectroscopy</topic><topic>Spectrum analysis</topic><topic>stability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Capelle, Martinus A. 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H</au><au>Gurny, Robert</au><au>Arvinte, Tudor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Throughput Protein Formulation Platform: Case Study of Salmon Calcitonin</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>26</volume><issue>1</issue><spage>118</spage><epage>128</epage><pages>118-128</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Purpose The feasibility of using high throughput spectroscopy for characterization and selection of physically stable protein formulations was studied. Materials and Methods A hundred aqueous formulations of salmon calcitonin (sCT) were prepared using 20 buffer compositions. The solutions had pH values between 2.5 and 10.5. The stability of the sCT formulations was analyzed over 1 week by the following assays: (1) protein concentration, (2) volume control by measuring pathlength, (3) turbidity (absorbance at 350 nm), (4) intrinsic tyrosine fluorescence, (5) 1-anilino-naphthalene-8-sulfonate (ANS) fluorescence, (6) Nile Red fluorescence. Addition of the dyes (Nile Red and ANS) was used to study protein conformational changes. Results After 1 day, 27 out of the 100 formulations of salmon calcitonin were stable. After 7 days, 12 stable sCT formulations remained. The best salmon calcitonin formulation was in 10 mM sodium acetate buffer with pH values between 3.5 and 5.5. Conclusions The findings are in accordance with the sCT formulations that were patented and used commercially. This can be considered as a proof of concept for the high throughput protein formulation platform.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>18600433</pmid><doi>10.1007/s11095-008-9662-8</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Anilino Naphthalenesulfonates - chemistry
Biochemistry
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Bone Density Conservation Agents - administration & dosage
Bone Density Conservation Agents - chemistry
Buffers
Calcitonin - administration & dosage
Calcitonin - chemistry
Chemistry, Pharmaceutical
Drug Evaluation, Preclinical - methods
Feasibility studies
Fluorescent Dyes
General pharmacology
high throughput screening
Hydrogen-Ion Concentration
Medical Law
Medical sciences
Oxazines
Pharmaceutical sciences
Pharmaceutical Solutions
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacy
protein formulation
Proteins
Research Paper
Salmon
salmon calcitonin
Spectrometry, Fluorescence
Spectrophotometry, Ultraviolet
spectroscopy
Spectrum analysis
stability
title High Throughput Protein Formulation Platform: Case Study of Salmon Calcitonin
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