The influence of hydrodynamics on the dissolution of poorly soluble drugs:
Saved in:
| Main Author: | |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
Aachen
Shaker
2002
|
| Series: | Berichte aus der Pharmazie
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zugl.: Frankfurt a.M., Johann Wolfgang Goethe-Univ., Diss., 2002 |
| Physical Description: | XVI, 170 S. Ill., graph. Darst. |
| ISBN: | 3832209069 |
Staff View
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Record in the Search Index
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| adam_text | THE INFLUENCE OF HYDRODYNAMICS ON THE DISSOLUTION OF POORLY SOLUBLE
DRUGS DISSERTATION ZUR ERLANGUNG DES DOKTORGRADES DER
NATURWISSENSCHAFTEN VORGELEGT BEIM FACHBEREICH CHEMISCHE UND
PHARMAZEUTISCHE WISSENSCHAFTEN DER JOHANN WOLFGANG GOETHE-UNIVERSITAET
FRANKFURT AM MAIN VON ANNETTE KERSTIN SCHOLZ (LUDWIGSHAFEN AM RHEIN)
FRANKFURT AM MAIN, 2002 TABLE OF CONTENTS ACKNOWLEDGEMENTS I TABLE OF
CONTENTS III LIST OF FIGURES - VII LIST OF TABLES X ABBREVIATIONS XIV 1
INTRODUCTION 1 1.1 ORAL BIOAVAILABILITY AND DISSOLUTION TESTING 2 1.2
DISSOLUTION KINETICS 5 1.2.1 DIFFUSION COEFFICIENT 5 1.2.2 SURFACEAREA 6
1.2.3 SOLUBILITY AND WETTING 6 1.2.4 CONCENTRATION OF DISSOLVED DRUG AT
TIME T (MT/V) 7 1.2.5 THE THICKNESS OF THE BOUNDARY LAYER 7 1.3
HYDRODYNAMICS AND MASS TRANSFER 7 1.4 RELEVANT GL - PHYSIOLOGY 10 1.5
THE ANIMAL MODEL 15 1.5.1 GENERAL CONSIDERATIONS 15 1.5.2 THE DOG MODEL
16 F.5.3 REQUIREMENTS OF THE STUDY 17 1.5.4 CHOICE OF THE MODEL 18 1.6
MODEL SUBSTANCE: FELODIPINE 19 1.6.1 PHARMACOLOGY/PHARMACOKINETICS 19
1.6.2 METABOLISM 19 1.6.3 PHYSICOCHEMICAL PROPERTIES 22 1.6.4 STABILITY
23 1.7 AIMS OF THE THESIS 24 2 MATERIALS AND METHODS 25 2.1 MATERIALS 26
2.1.1 CHEMICALS 26 2.1.2 GENERAL LABORATORY EQUIPMENT 29 2.1.3 HPLC/GC
SYSTEMS USED FOR ASSAYS 30 2.2 METHODS 32 2.2.1 ANIMALS 32 2.2.2 STUDY
PROTOCOL 33 2.2.2.1 CHYME STUDIES 34 2.2.2.2 PHARMACOKINETIC STUDIES 35
2.2.3 ANIMAL ETHICS APPROVAL 35 2.2.4 PREPARATION OF
SOLUTIONS/SUSPENSIONS 35 2.2.4.1 FOR IN VIVO EXPERIMENTS 35 2.2.4.2 FOR
IN VITRO EXPERINENTS 36 2.2.5 PH MEASUREMENTS 38 2.2.6 OSMOLALITY
MEASUREMENTS 38 2.2.7 PEG DETERMINATION 39 2.2.8 NET WATER FLUX 40 2.2.9
BILE SALT DETERMINATION 41 2.2.10 SOLUBILITY DETERMINATION 41 2.2.10.1
IN CANINE CHYME 41 2.2.10.2 IN SIMULATED INTESTINAL FLUIDS 42 2.2.10.3
IN 0.9 % NACI CONTAINING 0.8 % PEG 4000 42 2.2.11 FELODIPINE 43 2.2.11.1
HPLC ASSAY - NON EXTRACTION METHOD 43 2.2.11.2 HPLC ASSAY - EXTRACTION
METHOD 45 2.2.11.3 GC ASSAY 48 2.2.11.4 PARTICLE SIZE DISTRIBUTION 49
2.2.11.5 SURFACE AREA DETERMINATION 49 2.2.11.6 DIFFERENTIAL SCANNING
CALORIMETRY 50 2.2.12 DISSOLUTION STUDIES 50 2.3 DATA ANALYSIS AND
STATISTICAL METHODS 51 2.3.1 DATA SELECTION CRITERIA 51 2.3.2
PHARMACOKINETIC CALCULATIONS 51 2.3.3 DATA FITTING OF DISSOLUTION
STUDIES 52 2.3.4 F 2 FACTOR CALCULATION 53 2.3.5 IN VIVO-IN VITRO
COMPARISON S 54 IV 2.3.6 STATISTICS 54 3 RESULTS AND DISCUSSION 57 3.1
OPTIMISATION OF INFUSION SOLUTION AND ORAL SOLUTION TO SIMULATE A FED
LIKE MOTILITY PATTERN 58 3.1.1 INTRAJEJUNAL INFUSION 59 3.1.1.1 VOLUME
AND DELIVERY RATE OF THE INFUSION 59 3.1.1.2 SALINE INFUSION: INFLUENCE
OF CONCENTRATION 59 3.1.1.3 GLUCOSE INFUSION: INFLUENCE OF CONCENTRATION
61 3.1.2 ORAL SOLUTION 64 3.1.2.1 VOLUME OF THE ORAL SOLUTION 64 3.1.2.2
ORAL SALINE SOLUTION: INFLUENCE OF CONCENTRATION 65 3.1.2.3 ORAL GLUCOSE
SOLUTION: INFLUENCE OF CONCENTRATION 65 3.1.3 COMBINATION OF INFUSION
AND PERORAL SOLUTION 69 3.1.4 SUMMARY 70 3.2 PH 71 3.2.1 ADMINISTERED
SOLUTIONS 71 3.2.2 CHYME 71 3.3 OSMOLALITY 75 3.3.1 ADMINISTERED
SOLUTIONS 75 3.3.2 CHYME 75 3.4 DETECTION OF MOTILITY PHASE BY NWF AND
COLOUR 78 3.4.1 CUMULATIVE NET WATER FLUX 78 3.4.2 NET WATER FLUX 80 3.5
BILE SALTS 84 3.6 SOLUBILITY 84 3.6.1 IN 0.9 % NACI CONTAINING 0.8 % PEG
4000 84 3.6.2 IN CANINE CHYME 84 3.6.3 IN SIMULATED INTESTINAL FLUIDS 85
3.6.4 PARTICIE SIZE EFFECTS ON THE RATE OF APPROACH TO THE EQUILIBRIUM
SOLUBILITY 87 3.7 CHYME FLOW CHARACTERISTICS 88 3.7.1 TJ4 TO MIDGUT 88
3.7.2 DIFFERENTIAL RATE OF ARRIVAL OF CHYME AT MIDJEJUNUM 91 3.8
CONCENTRATION OF DISSOLVED FELODIPINE IN CHYME 95 V 3.8.1 MICRONIZED
POWDER 95 3.8.2 COARSE GRADE POWDER 104 3.9 PHARMACOKINETICS 105 3.9.1
INFLUENCE OF PARTICIE SIZE ON FELODIPINE ABSORPTION 108 3.9.2 INFLUENCE
OF HYDRODYNAMICS ON FELODIPINE ABSORPTION 109 3.9.3 CONCLUSION 112 3.10
DISSOLUTION STUDIES - 113 3.10.1 COMPARISON OF RESUITS FOR MICRONIZED
AND COARSE FELODIPINE 114 3.11 MATHEMATICAL EVALUATION OF THE
DISSOLUTION DATA 116 3.11.1 MODEL DEPENDENT DATA FITTING 116 3.11.2
MODEL INDEPENDENT F 2 FACTOR CALCULATION 119 3.12 IN VIVO-IN VITRO
COMPARISONS 121 4 SUMMARY 125 5 ZUSAMMENFASSUNG UND AUSBLICK 129 6
APPENDICES 135 6.1 INDIVIDUAL CHYME DATA 136 6.1.1 SALINE EXPERIMENTS
136 6.1.2 GLUCOSE EXPERIMENTS 139 6.2 LINEAR REGRESSION OF CDF VS. V AND
V VS. T 142 6.3 INDIVIDUAL PLASMA DATA 143 6.3.1 SALINE EXPERIMENTS 143
6.3.2 GLUCOSE EXPERIMENTS 146 6.4 PARTICIE SIZE DISTRIBUTION AND SURFACE
AREA 149 6.5 DSC DATA OF FELODIPINE 150 7 BIBLIOGRAPHY 153 8 CURRICULUM
VITAE 167 VI
|
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| indexdate | 2024-07-09T19:10:36Z |
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| isbn | 3832209069 |
| language | English |
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| physical | XVI, 170 S. Ill., graph. Darst. |
| publishDate | 2002 |
| publishDateSearch | 2002 |
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| publisher | Shaker |
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| series2 | Berichte aus der Pharmazie |
| spelling | Scholz, Annette Verfasser aut The influence of hydrodynamics on the dissolution of poorly soluble drugs Annette Scholz Aachen Shaker 2002 XVI, 170 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Berichte aus der Pharmazie Zugl.: Frankfurt a.M., Johann Wolfgang Goethe-Univ., Diss., 2002 Tiermodell (DE-588)4140660-6 gnd rswk-swf Gastrointestinaltrakt (DE-588)4074445-0 gnd rswk-swf Wasserlöslichkeit (DE-588)4273707-2 gnd rswk-swf Hydrodynamik (DE-588)4026302-2 gnd rswk-swf Wirkstofffreisetzung (DE-588)4190018-2 gnd rswk-swf Arzneimittel (DE-588)4003115-9 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Arzneimittel (DE-588)4003115-9 s Wasserlöslichkeit (DE-588)4273707-2 s Wirkstofffreisetzung (DE-588)4190018-2 s Gastrointestinaltrakt (DE-588)4074445-0 s Hydrodynamik (DE-588)4026302-2 s Tiermodell (DE-588)4140660-6 s DE-604 GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010169953&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Scholz, Annette The influence of hydrodynamics on the dissolution of poorly soluble drugs Tiermodell (DE-588)4140660-6 gnd Gastrointestinaltrakt (DE-588)4074445-0 gnd Wasserlöslichkeit (DE-588)4273707-2 gnd Hydrodynamik (DE-588)4026302-2 gnd Wirkstofffreisetzung (DE-588)4190018-2 gnd Arzneimittel (DE-588)4003115-9 gnd |
| subject_GND | (DE-588)4140660-6 (DE-588)4074445-0 (DE-588)4273707-2 (DE-588)4026302-2 (DE-588)4190018-2 (DE-588)4003115-9 (DE-588)4113937-9 |
| title | The influence of hydrodynamics on the dissolution of poorly soluble drugs |
| title_auth | The influence of hydrodynamics on the dissolution of poorly soluble drugs |
| title_exact_search | The influence of hydrodynamics on the dissolution of poorly soluble drugs |
| title_full | The influence of hydrodynamics on the dissolution of poorly soluble drugs Annette Scholz |
| title_fullStr | The influence of hydrodynamics on the dissolution of poorly soluble drugs Annette Scholz |
| title_full_unstemmed | The influence of hydrodynamics on the dissolution of poorly soluble drugs Annette Scholz |
| title_short | The influence of hydrodynamics on the dissolution of poorly soluble drugs |
| title_sort | the influence of hydrodynamics on the dissolution of poorly soluble drugs |
| topic | Tiermodell (DE-588)4140660-6 gnd Gastrointestinaltrakt (DE-588)4074445-0 gnd Wasserlöslichkeit (DE-588)4273707-2 gnd Hydrodynamik (DE-588)4026302-2 gnd Wirkstofffreisetzung (DE-588)4190018-2 gnd Arzneimittel (DE-588)4003115-9 gnd |
| topic_facet | Tiermodell Gastrointestinaltrakt Wasserlöslichkeit Hydrodynamik Wirkstofffreisetzung Arzneimittel Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010169953&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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