Lyophilization of nucleic acid nanoparticles: formulation developement, stabilization mechanisms, and process monitoring
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
München
Dr. Hut
2012
|
| Edition: | 1. Aufl. |
| Series: | Pharmazeutische Technologie
|
| Subjects: | |
| Online Access: | Inhaltstext Inhaltsverzeichnis |
| Physical Description: | XXII, 314 S. graph. Darst. 210 mm x 148 mm, 503 g |
| ISBN: | 9783843905695 384390569X |
Staff View
MARC
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Record in the Search Index
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IMAGE 1
TABLE OF CONTENTS
XIII
TABLE OF CONTENTS
ACKNOWLEDGMENT IV
TABLE OF CONTENTS XII
LIST OF ABBREVIATIONS XIX
CHAPTER 1
GENERAL INTRODUCTION 1
ABSTRACT 2
1 LYOPHILIZATION IN BRIEF 3
1.1 THE LYOPHILIZATION PROCESS 3
1.2 THE LYOPHILIZATION EQUIPMENT 8
2 RECENT ADVANCES AND FURTHER CHALLENGES IN LYOPHILIZATION 11
2.1 LYOPHILIZATION BEYOND THE DRYING OFPHARMACEUTICAL PROTEINS 11
2.2 PHARMACEUTICAL APPLICATIONS OF/YOPHILISATES IN THE SOLID STATE 12
2.3 NOVEL FORMULATION ASPECTS 13
2.4 IMPORTANCE O F THE FIREEZING STEP IN LYOPHILIZATION 14
2.5LYOPHILIZATION ABOVE TG' 15
2.6 STABUIZATION BY THERMAL TREATMENT/HIGH SECONDARY DRYING TEMPERATURES
16
2.7INDIVIDUALFACTORS CONTRIBUTINGTOPROTEIN STABILITYDURINGLYOPHILIZATION
17
2.8 BNHANCED UNDERSTANDING O F STABI/IZATION MECHANISMS IN THE SOLID
STATE 18
2.9 QUALITY BY DESIGN AND PROCESS ANALYTICAL TECHNOLOGY IN
LYOPHILIZATION 19
2.10 NOVEL CONTAINER SYSTEMS 21
2.11 SCALE-UP EQUIPMENT ISSUES AND THE DREAM OFCONTINUOUS PROCESSING 23
2.12 CONDUSION AND OUTLOOK 24
3 LYOPHILIZATION OF NUCLEIC ACID NANOPARTICLES 25
3.1 PDNA AND SIRNA DEIIVERY IN GENE THERAPY AND THE NEED FOR TONG-TERM
STABLE FORMUIATIONS 25
3.2 THE CURRENT STATUS ON LYOPHILIZATION O F NUCLEIC ACID NANOPARTICLES
28
4 REFERENCES 34
HTTP://D-NB.INFO/1025018311
IMAGE 2
XIV TABLE OF CONTENTS
CHAPTER 2
THE FREEZING STEP IN LYOPHILIZATION 51
ABSTRACT 52
1 INTRODUCTION 53
2 PHYSICO-CHEMCIAL FUNDAMENTALS OF FREEZING 55
2.1 FREEZINGPHENOMENA: SUPERCOOLING, ICE NUCLEATION AND ICE CRYSTAL
FORMATION . 55 2.2 CRYSTALLIZATION AND VITRIFICATION O F SOLUTES 59
2.3 PHASE SEPARATION AND OTHER TYPES O F FREEZING BEHAVIOR 63
3 MODIFICATIONS OF THE FREEZING STEP 65
3.1 SHEIF-RAMPED FREEZING 65
3.2 PRE-COOIED SHEIF METHOD 67
3.3ANNEALING 67
3.4 QUENCH FREEZING 69
3.5 DIRECTIONALFREEZING 69
3.6 ICE FOG TECHNIQUE 70
3.7 ELECTROFREEZING 70
3.8 UITRASOUND-CONTROILED ICE NUCLEATION 72
3.9 VACUUM-INDUCEDSURFACE FREEZING 74
3.10 HIGH PRESSURE SHIFT FREEZING OR DEPRESSURIZATION TECHNIQUE 75 3.11
ADDITION O F ICE NUCLEATION AGENTS 76
3.12 NON-AQUEOUS CO-SOLVENTS 77
3.13 OTHERS 79
4 CONSEQUENCES OF THE FREEZING STEP ON GENERAL QUALITY ATTRIBUTES
OF BIOPHARMACEUTICALS AND PROCESS PERFORMANCE 80
4.1 INTRA-VIAL AND INTER-VIAL UNIFORMITY 80
4.2 SAMPLE MORPHOLOGY 83
4.3 PRIMARY AND SECONDARY DRYING PERFORMANCE 84
4.4 PHYSICAL STATE O F THE SAMPLE 89
4.5RESIDUALMOISTURE CONTENT 90
4.6 RECONSTITUTION TIME 91
5 CONSEQUENCES OF THE FREEZING STEP ON PROTEIN STABILITY 93
5.1 GENERAL STRESS FACTORS DURING FREEZING 93
5.2 INFLUENCE OFTHE FREEZING STEP ON PROTEIN STABILITY 97
6 CONCLUSION AND PRACTICAL CONSIDERATION 101
7 REFERENCES 104
CHAPTER 3
OBJECTIVESOFTHE THESIS 113
IMAGE 3
TABLE OF CONTENTS XV
CHAPTER 4
ESTABLISHMENT OF AN UP-SCALED MICRO-MIXER METHOD 115
ABSTRACT 116
1 INTRODUCTION 117
2 MATERIALS AND METHODS 119
2.1 MATERIALS 119
2.2 PREPARATION OFPLASMID/LPEI POLYP/EXES BY PIPETTING 119
2.3 UP-SCALED PREPARATION OFPLASMID/LPEI POLYPLEXES 119
2.4 PARTIDE SIZE DETERMINATION 120
2.5 CELL CULTURE 120
3 RESULTS AND DISCUSSION 122
3.1 ESTABLISHMENT OFTHE UP-SCALED MICRO-MIXER METHOD FOR THE PREPARATION
O F PLASMID/LPEI POLYPLEXES 122
3.2 INFFUENCE OFTHE PLASMID CONCENIRATION ON PARTIDE SIZE AND
POTYDISPERSITY O F PLASMID/LPEI POLYPLEXES 125
4CONCLUSION 127
5 REFERENCES 128
CHAPTER 5
DEVELOPMENT OF A LYOPHILIZED PLASMID/LPEI POLYPLEX FORMULATION WITH
LONG-TERM STABILITY 129
ABSTRACT 130
11NTRODUCTION 132
2 MATERIALS AND METHODS 135
2.1 MATERIALS 135
2.2 PREPARATION O F PLASMID/LPEI POLYPLEXES 135
2.3 FREEZE-THAWING STUDIES 135
2.4 LYOPHIIIZATION O F PLASMID/LPEI POLYPLEXES 136
2.5 LONG-TERM STABIIITY 136
2.6 PLASMID/LPEI POLYPLEX CHARACTERIZATION 136
2.70SMOMETRY 137
2.8 TURBIDIMETRY 137
2.9 LIGHT OBSCURATION 137
2.10 CELL CULTURE: CYTOTOXICITY AND IUDFERASE REPORTERGENE EXPRESSION
137
2.11 KARL FISCHER TITRATION 138
2.12 DIFFERENTIAL SCANNING CALORIMETRY (DSC) 138
2.13 X-RAY POWDER DIFFRACTION (XRD) 139
IMAGE 4
XVI
TABLE OF CONTENTS
2.14 STATISTICAL ANA/YS/S 139
3 RESULTS 140
3.1 INFLUENAE O F (HE BUFFER COMPOSITION 140
3.2 FREEZE-THAWING STUDIES 141
3.3 PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES OFLYOPHILIZED
PLASMID/LPEI POLYPLEXES 144
3.4 PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES O F LYOPHILIZED
PLASMID/LPEI POLYPLEXES AFTER STORAGE 150
4 DISCUSSION 152
5 CONCLUSION 161
6 REFERENCES 163
CHAPTER 6
INVESTIGATIONS ON POLYPLEX STABILITY DURING THE FREEZING STEP OF
LYOPHILIZATION
USING CONTROLLED ICE NUCLEATION 167
ABSTRACT 168
1 INTRODUCTION 170
2 MATERIALS AND METHODS 175
2.1 MATERIALS 175
2.2 SAMPLE PREPARATION 175
2.3 FREEZE-THAW STUDIES USING DIFFERENT FREEZING PROTOCOLS 176
2.3.1 CONVENTIONAL SHELF-RAMP FREEZING 176
2.3.2 'STANDARD' DEPRESSURIZATION METHOD 177
2.3.3 VARYING ICE NUCLEATION TEMPERATURES VIA CONTROLLED ICE NUCLEATION
177
2.3.4 VARYING SHELF-RAMP RATES AFTER CONTROLLED ICE NUCLEATION 177
2.3.5 INTERRUPTION OF THE FREEZING PROCESS AFTER CONTROLLED ICE
NUCLEATION 178
2.4 LYOPHILIZATION 178
2.5POLYPLEX CHARACTERIZATION 178
2.6 SPECIFIC SURFACE AREA DETERMINATION 179
2.7 KARL-FISCHER TITRATION 179
2.8 THEORETICALMODEIING OFTHE CHANGE IN SUCROSE CONCENTRATION OR
VISCOSITY DURING FREEZE-CONCENTRATION AND CORRELATION TO REACTION RATES
180
2.9 STATISTICAL ANALYSIS 183
3 RESULTS 184
3.11NFLUENCE OFTHE 'STANDARD' DEPRESSURIZATION METHOD IN COMPARISON TO
CONVENTIONAL SHEIF-RAMP FREEZING ON POLYPLEX STABILITY 184
3.2 INFLUENAE O F ICE NUCLEATION TEMPERATURE ON POLYPLEX STABILITY 188
3.3 INFLUENCE OFRESIDENCE TIME ON POLYPLEX STABILITY 190
3.4 INFLUENCE OFTHE PROCEEDING O F FREEZING ON POLYPLEX STABILITY 192
IMAGE 5
TABLE OF CONTENTS
XVII
3.5 SURFACE AREA AND RESIDUAL MOISTURE CONTENT OFSELECTED LYOPHILIZED
SAMP/ES 194
3.6 THEORETICALMODE/ING OFTHE CHANGE IN SUCROSE CONCENTRATION OR
VISCOSITY DURING FREEZE-CONCENTRATION AND CORREIATION TO REACTION RATES
196
4 DISCUSSION 200
5 SUMMARY AND CONCLUSION 212
6 REFERENCES 214
CHAPTER 7
FORMULATION DEVELOPMENT OF LYOPHILIZED, LONG-TERM STABLE
SIRNA/OLIGOAMINOAMIDE POLYPLEXES 219
ABSTRACT 220
1 INTRODUCTION 221
2 MATERIALS AND METHODS 225
2.1 MATERIALS 225
2.2 PREPARATION OFSIRNA POLYPLEXES 226
2.3 FREEZE-THAWING STUDIES 227
2.4 LYOPHFFIZATION OFSIRNA POLYPLEXES 227
2.5 LONG-TERM STABILITY TESTING O F LYOPHILIZED SAMPLES 227
2.6RECONSTITUTION OFLYOPHILIZEDSAMPLES 228
2.7 SIRNA POLYPLEX CHARACTERIZATION 228
2.8 CELL CULTURE: METABOLIC ACTIVITY ANDGENE SILENCING 228
2.90SMOMETRY 229
2.10 TURBIDIMETRY 230
2.11 LIGHT OBSCURATION 230
2.12 KARI FISCHER TTTRATICM 230
2.13 DIFFERENTIAL SCANNING CALORIMETRY (DSC) 231
2.14 X-RAYPOWDER DIFFRACTION (XRD) 231
2.15 STATISTICAL ANALYSIS 231
3 RESULTS 232
3.1 UP-SCALED PREPARATION AND CHARACTERIZATION OFSIRNA POLYPLEXES 232
3.2 FREEZE-THAWING STUDIES 233
3.3 LYOPHUIZATION O F SIRNA/OLIGOAMINOAMIDE POLYPLEXES 238
3.4 LONG-TERM STABILITY O F LYOPHILIZED SIRNA/OLIGOAMINOAMIDE POLYPLEXES
241
4 DISCUSSION 247
5 CONCLUSION 257
6 REFERENCES 259
IMAGE 6
XVIII
TABLE OF CONTENTS
CHAPTER 8
IMPLEMENTATION AND EVALUATION OF AN OPTICAL FIBER SYSTEM AS NOVEL
PROCESS
MONITORING TOOL DURING LYOPHILIZATION 265
ABSTRACT 266
1 INTRODUCTION 267
2 MATERIALS AND METHODS 272
2.1 MATERIALS 272
2.2 THE OPTICAL UEBER SYSTEM 272
2.2.1 OPTICAL FIBER SENSOR (OFS) STRUCTURE AND CHARACTERISTICS 272
2.2.2 OPERATION PRINCIPLE 274
2.2.3 SYSTEM AND DESIGN VARIATIONS 275
2.3 TEMPERATURE CALIBRATION 277
2.4 MEASUREMENT OFPRODUCT TEMPERATURE PROFILES DURING LYOPHILIZATION
AND FIREEZING EXPERIMENTS 278
2.5 DIFFERENTIAL SCANNING CALORIMETRY 279
3 RESULTS AND DISCUSSION 280
3.1 PRODUCT TEMPERATURE MEASUREMENTS AND END POINT DETECTION 278 3.2
SENSITIVITY TO PHYSICO-CHEMICAL EVENTS DURING FREEZING 281
3.2.1 SUPERCOOLING AND ICE NUCLEATION 281
3.2.2 CRYSTALLIZATION OF EXCIPIENTS 283
3.2.3 GIASS FORMATION OF EXCIPIENTS 285
3.3 INFLUENAE OFTHE SHIELDING OR UNSHIELDING OFTHE OFSS ON TEMPERATURE
PROFILES 288
3.4 THREE-DIMENSIONAL INFORMATION ON TEMPERATURE PROFILES IN A VIAL 289
3.5 NON-IN VASIVE TEMPERATURE PROFILING DURING LYOPHILIZATION 293
4 CONCLUSION 297
5 REFERENCES 299
CHAPTER 9
SUMMARY OF THE THESIS 303
APPENDIX 308
CURRICULUM VITAE 314 |
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| ctrlnum | (OCoLC)815953703 (DE-599)DNB1025018311 |
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| dewey-ones | 615 - Pharmacology and therapeutics |
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| dewey-sort | 3615.19 |
| dewey-tens | 610 - Medicine and health |
| discipline | Chemie / Pharmazie Medizin |
| edition | 1. Aufl. |
| format | Thesis Book |
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| indexdate | 2024-08-21T00:14:42Z |
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| publishDate | 2012 |
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| publisher | Dr. Hut |
| record_format | marc |
| series2 | Pharmazeutische Technologie |
| spelling | Kasper, Julia Christina Verfasser aut Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring Julia Christina Kasper 1. Aufl. München Dr. Hut 2012 XXII, 314 S. graph. Darst. 210 mm x 148 mm, 503 g txt rdacontent n rdamedia nc rdacarrier Pharmazeutische Technologie Zugl.: München, Ludwig-Maximilians-Univ., Diss., 2012 Pharmazeutische Chemie (DE-588)4132158-3 gnd rswk-swf Gentherapie (DE-588)4296957-8 gnd rswk-swf Gefriertrocknung (DE-588)4156264-1 gnd rswk-swf Nanopartikel (DE-588)4333369-2 gnd rswk-swf Nucleinsäuren (DE-588)4172117-2 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Nanopartikel (DE-588)4333369-2 s Nucleinsäuren (DE-588)4172117-2 s Gefriertrocknung (DE-588)4156264-1 s Gentherapie (DE-588)4296957-8 s Pharmazeutische Chemie (DE-588)4132158-3 s DE-604 X:MVB text/html http://deposit.dnb.de/cgi-bin/dokserv?id=4099018&prov=M&dok_var=1&dok_ext=htm Inhaltstext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025329315&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Kasper, Julia Christina Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring Pharmazeutische Chemie (DE-588)4132158-3 gnd Gentherapie (DE-588)4296957-8 gnd Gefriertrocknung (DE-588)4156264-1 gnd Nanopartikel (DE-588)4333369-2 gnd Nucleinsäuren (DE-588)4172117-2 gnd |
| subject_GND | (DE-588)4132158-3 (DE-588)4296957-8 (DE-588)4156264-1 (DE-588)4333369-2 (DE-588)4172117-2 (DE-588)4113937-9 |
| title | Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring |
| title_auth | Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring |
| title_exact_search | Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring |
| title_full | Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring Julia Christina Kasper |
| title_fullStr | Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring Julia Christina Kasper |
| title_full_unstemmed | Lyophilization of nucleic acid nanoparticles formulation developement, stabilization mechanisms, and process monitoring Julia Christina Kasper |
| title_short | Lyophilization of nucleic acid nanoparticles |
| title_sort | lyophilization of nucleic acid nanoparticles formulation developement stabilization mechanisms and process monitoring |
| title_sub | formulation developement, stabilization mechanisms, and process monitoring |
| topic | Pharmazeutische Chemie (DE-588)4132158-3 gnd Gentherapie (DE-588)4296957-8 gnd Gefriertrocknung (DE-588)4156264-1 gnd Nanopartikel (DE-588)4333369-2 gnd Nucleinsäuren (DE-588)4172117-2 gnd |
| topic_facet | Pharmazeutische Chemie Gentherapie Gefriertrocknung Nanopartikel Nucleinsäuren Hochschulschrift |
| url | http://deposit.dnb.de/cgi-bin/dokserv?id=4099018&prov=M&dok_var=1&dok_ext=htm http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025329315&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT kasperjuliachristina lyophilizationofnucleicacidnanoparticlesformulationdevelopementstabilizationmechanismsandprocessmonitoring |