La lecture à portée de main
Description
Sujets
Informations
Publié par | heinrich-heine-universitat_dusseldorf |
Publié le | 01 janvier 2009 |
Nombre de lectures | 76 |
Langue | Deutsch |
Poids de l'ouvrage | 8 Mo |
Extrait
Paediatric formulations of L-arginine for the
use in urea cycle disorders
Inaugural-Dissertation
zur Erlangung des Doktorgrades
der Mathematisch-Naturwissenschaftlichen Fakultät
der Heinrich-Heine-Universität Düsseldorf
vorgelegt von
Qaed Abdul Hussein
aus Baghdad
Düsseldorf, September 2009
aus dem Institut für Pharmazeutische Technologie und Biopharmazie
der Heinrich-Heine Universität Düsseldorf
Gedruckt mit der Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät
der Heinrich-Heine-Universität Düsseldorf
Referent: Prof. Dr. J. Breitkreutz
Koreferent: Prof. Dr. P. Kleinebudde
Tag der mündlichen Prüfung: 15.09.2009
Index I
Abbreviations VI
A Introduction and aim of the study 1
1. Introduction 1
2. Aim of the study 4
B General Part 5
1. Therapeutic uses of L-Arginine 5
2. Transduction mechanisms and types of taste 11
2.1 Bitter taste 11
2.2 Sweet taste 12
2.3 Salt taste 12
2.4 Acid taste 13
2.5 Umami taste 13
2.6 Fat taste 13
2.7 Water 14
3. Taste masking technologies 14
3.1 Taste masking with flavours, sweeteners, and amino acids 14
3.2 Taste masking with lipophilic vehicles 17
3.2.1 Lipids 17
3.2.2 Lecithin and lecithin-like substances 17
3.3 Taste masking by physical barriers 17
3.3.1 Carbohydrates 18
3.3.2 Zeolites 18
3.4 Taste masking by inclusion complexation 18
3.5 Taste masking by ion-exchange resins 19
4. Taste masking assessment 19
4.1 In vivo approaches for taste assessment 19
4.1.1 Human taste panel studies 19
4.1.2 Animal preference tests 21
4.1.3 Electrophysiological methods 21
I 4.2 In vitro approaches for taste assessment 21
4.2.1 In vitro drug release studies 22
4.2.2 In vitro assay methods 22
4.3 Biomimetic taste sensing systems 23
4.3.1 Lipid membrane taste sensors 25
4.3.2 The taste-sensing systems SA401 and SA402 25
4.3.3 Astree electronic tongue 25
4.3.4 Ion-sensitive field effect transistors 26
4.3.5 Voltammetric sensors 27
4.3.6 Alternative electronic tongue 27
C Results and Discussion 28
1. L-arginine HCL 10% solution 28
1.1 Introduction 28
1.2 Formulation development 30
1.3 Taste masking of L-arginine in solution 33
1.4 First preformulation study 35
1.5 Second preformulation study 41
1.6 Long-term stability study 46
1.7 In-use stability test 50
1.8 Conclusion 53
2. Multiparticulate formulations 54
2.1 Extrusion/spheronisation process 54
2.1.1 Introduction 54
2.2 Wet Extrusion 56
2.2.1 MCC and HPMC 56
2.3 Solid Lipid Extrusion 58
2.3.1 Formulation variation 60
2.3.2 Process parameters 61
2.3.3 Spheronization 63
2.3.4 Pellet shape, size and size distribution 67
II 2.4 L-arginine free base dissolution 70
2.4.1 Dissolution media and process parameter 70
2.4.2 Self-coating of the lipid pellets 75
2.4.5 Stability of lipid pellets 82
2.4.6 Conclusion 94
3. Taste assessment 96
3.1 Taste analysis of different solution formulations 96
3.2 Taste analysis of primary formulations 97
3.2.1 Insent taste sensing system SA402B 98
3.3 Effects of pH and ionic strength on the taste assessment 104
3.4 Taste analysis of 10% L-arginine HCL formulations 114
3.4.1 Insent taste sensing system SA402B 114
3.4.2 Human taste panel 117
3.4.3 Correlation taste panel to electronic tongue data 118
3.5 Conclusion 120
D Summary 121
E Zusammenfassung 124
F Experimental Part 127
1. Materials 127
1.1 L-arginine 127
1.1.1 Characterization of L-arginine 127
1.1.1.1 Physical properties 127
1.1.1.1.1 X-Ray Powder Diffraction Pattern 127
1.1.1.1.2 Particle Morphology 128
1.1.1.1.3 Thermal Methods of Analysis 129
1.1.1.1.3.1 Melting Behaviour 129
1.1.1.1.3.2 Differential Scanning Calorimetry 129
1.1.1.1.4 Hygroscopicity 129
1.1.1.1.5 Solubility characteristics 129
1.1.1.1.6 Ionization Constants 130
III 1.1.1.1.7 Spectroscopy 130 1.1.1.1.7.1 Vibrational Spectroscopy 130
1.1.1.1.7.2 Nuclear Mag