In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin:
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| Format: | Thesis Book |
| Language: | English |
| Published: |
Bonn
2017
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | VII, 204 Seiten Diagramme, Illustrationen |
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| 245 | 1 | 0 | |a In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin |c vorgelegt von Samiha Omar Abduarhman Mouftah |
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| 502 | |b Dissertation |c Rheinische Friedrich-Wilhelms Universität Bonn |d 2017 | ||
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| adam_text | TABLE OF CONTENTS
1 INTRODUCTION AND AIM OF
WORK.......................................................................1
2 THEORETICAL
BACKGROUND..................................................................................8
2.1
HEPARIN.............................................................................................................................
8
2.1.1 STRUCTURE, MECHANISM OF ACTION AND THERAPEUTIC EFFECTS
.........................................
8
2.1.2 DIFFERENT STRATEGIES OF NON-INVASIVE LMWH
DELIVERY...........................................11
2.2 BUCCAL
MUCOSA................................................................................................................16
2.2.1 OVERVIEW OF THE ORAL M UCOSA
..................................................................................
16
2.2.1.1 STRUCTURE OF ORAL
MUCOSA......................................................................................
16
2.2.1.2 PERMEABILITY OF ORAL MUCOSA
...............................................................................
18
2.2.2 DRUG DELIVERY VIA THE BUCCAL
MUCOSA.....................................................................19
2.2.3 EXPERIMENTAL METHODOLOGY FOR STUDYING BUCCAL MUCOSA DRUG
ABSORPTION...........20
2.2.3.1 IN VITRO
METHODS...................................................................................................
20
2.2.3.2 IN VIVO
METHODS...................................................................................................20
2.3
NANOPARTICLES................................................................................................................
21
2.3.1 MUCOADHESIVE POLYMERIC
NANOPARTICLES................................................................
22
2.3.2 PREPARATION OF POLYMERIC
NANOPARTICLES.................................................................
24
2.3.2.1 EMULSIFICATION SOLVENT EVAPORATION
TECHNIQUE................................................... 24
2.3.2.2 EMULSIFICATION SOLVENT DIFFUSION
TECHNIQUE.......................................................26
2.3.2.3 SOLVENT DISPLACEMENT
TECHNIQUE.........................................................................
27
2.3.3 EVALUATION OF THE INTERACTIONS OF NANO-AND MICROPARTICLES WITH
MUCUS
..............
29
2.3.3.1 IN VITRO
METHODS...................................................................................................
29
2.3.3.2 EX VIVO
METHODS..................................................................................................
31
2.3.3.3 IN VIVO
METHODS...................................................................................................
31
I
2.4
LYOPHILIZATION................................................................................................................
32
2.4.1 LYOPHILIZATION
PROCESS...........................................................................................
32
2.4.1.1
FREEZING...............................................................................................................
33
2.4.1.2 PRIMARY
DRYING.....................................................................................................
34
2.4.1.3 SECONDARY
DRYING.................................................................................................
34
2.4.2 LYOPHILIZATION OF
NANOPARTICLES.............................................................................
34
2.4.3 PHARMACEUTICAL APPLICATION OF LYOPHILIZATION IN THE DEVELOPMENT OF
SOLID DOSAGE
FORMS........................................................................................................................................37
3 MATERIALS AND
METHODS...................................................................................40
3.1
MATERIALS........................................................................................................................
40
3.1.1 LOW MOLECULAR WEIGHT HEPARIN (LM W
H).............................................................40
3.1.2 M
UCIN......................................................................................................................
40
3.1.3 AMMONIO METHACRYLATE COPOLYMER (AM C)
.........................................................
42
3.1.4 ETHYL
CELLULOSE........................................................................................................
42
3.1.5 ETHYL
ACETATE............................................................................................................43
3.1.6 POLYETHYLENE GLYCOLS (PEGS)
.................................................................................
43
3.1.7 POLYVINYL ALCOHOL
(PVA)........................................................................................44
3.1.8
TREHALOSE.................................................................................................................44
3.1.9 M
ANNITOL..................................................................................................................45
3.1.10
LACTOSE....................................................................................................................45
3.1.11 POLYVINYL PYRROLIDONE
(PVP).................................................................................
45
3.2 POLYMERIC NANOPARTICLES
PREPARATION........................................................................46
3.2.1 PREPARATION OF DRUG-FREE NANOPARTICLES BY MODIFIED SOLVENT
DIFFUSION-
EVAPORATION
TECHNIQUE...........................................................................................................
46
3.2.2 PREPARATION OF LMWH NANOPARTICLES BY MODIFIED SOLVENT
DIFFUSION-EVAPORATION
TECHNIQUE.................................................................................................................................46
3.2.3 PREPARATION OF LMWH NANOPARTICLES BY MODIFIED SOLVENT DISPLACEMENT
TECHNIQUE.................................................................................................................................
48
3.3 ANALYTICAL
METHODS.......................................................................................................
49
3.3.1 DETERMINATION OF NANOPARTICLE SIZE AND ZETA
POTENTIAL......................................... 49
3.3.2 DETERMINATION OF LMWH ENTRAPMENT EFFICIENCY AND NANOPARTICLES
RECOVERY... 49
3.3.3 DROP SHAPE
ANALYSIS.................................................................................................50
3.3.4 SCANNING ELECTRON MICROSCOPY (SEM)
...................................................................
51
3.3.5 FLUORESCENCE LABELING OF LMWH
MOLECULES.........................................................51
3.3.6 IN VITRO LMWH RELEASE
STUDIES..............................................................................52
3.3.6.1 PREPARATION OF MUCIN
SAMPLES............................................................................52
3.3.6.2 HEPARIN RELEASE TEST
.............................................................................................
53
3.3.63 ACTICHROME HEPARIN (ANTI-FXA)
ASSAY.....................................................53
3.3.7 RHEOLOGICAL
MEASUREMENTS.....................................................................................
54
3.3.8 RESIDUAL PEG
CONTENT.............................................................................................
55
3.3.9 EX VIVO PERMEATION
STUDIES....................................................................................
55
3.3.9.1 TISSUE
PREPARATION...............................................................................................55
3.3.9.2 DRUG PERMEATION STUDY THROUGH PORCINE BUCCAL M
UCOSA.................................56
3.3.10 CONFOCAL MICROSCOPE
ANALYSIS................................................................................57
3.4 LYOPHILIZATION OF
NANOPARTICLES..................................................................................
58
3.4.1 LYOPHILIZATION
PROCESS...........................................................................................
58
3.4.2 RECONSTITUTION OF THE LYOPHILIZED POLYMERIC
NANOPARTICLES..................................59
3.4.3 LONG-TERM STABILITY OF LYOPHILIZED NANOPARTICLES POW
DER....................................59
3.4.4 PREPARATION OF BUCCAL LYOPHILISATES
.......................................................................
59
3.5 CHARACTERIZATION OF BUCCAL LYOPHILISATES
...................................................................
60
3.5.1 BUCCAL LYOPHILISATES DISINTEGRATION TIM E
............................................................... 60
3.5.2 SCANNING ELECTRON MICROSCOPE ANALYSIS OF BUCCAL LYOPHILISATES
..........................
61
3.5.3 MOISTURE
ANALYSIS.....................................................................................................61
3.5.4 DISSOLUTION STUDIES
61
3.5.5 STABILITY STUDIES OF BUCCAL LYOPHILISATE
...............................................................
61
3.6 STATISTICAL
ANALYSIS.........................................................................................................62
4 RESULTS AND
DISCUSSION...................................................................................63
4.1 PREPARATION OF LMWH NANOPARTICLES BY MODIFIED SOLVENT
DIFFUSION-EVAPORATION
METHOD.......................................................................................................................................
63
4.1.1 METHOD
DEVELOPMENT..............................................................................................
63
4.1.2 PROCESS PARAMETERS AND NANOPARTICLES
MORPHOLOGY............................................. 64
4.1.2.1 EFFECT OF POLYMER
AMOUNT...................................................................................64
4.1.2.2 EFFECT O F HEPARIN
AMOUNT....................................................................................66
4.1.2.3 EFFECT OF SURFACTANT
CONCENTRATION......................................................................
69
4.1.3 DROP SHAPE
ANALYSIS................................................................................................
74
4.1.4 IN VITRO RELEASE
STUDY..............................................................................................
75
4.1.5 RHEOLOGICAL MUCOADHESION M
ETHOD......................................................................
78
4.2 PREPARATION OF LMWH NANOPARTICLES BY MODIFIED SOLVENT DISPLACEMENT
METHOD
85
4.2.1 METHOD
DEVELOPMENT..............................................................................................
85
4.2.2 PROCESS PARAMETERS AND NANOPARTICLES MORPHOLOGY
.............................................
86
4.2.2.1 EFFECT OF POLYMER AMOUNT
..................................................................................
90
4.2.2.2 EFFECT OF SURFACTANT
CONCENTRATION......................................................................
91
4.2.2.3 EFFECT OF HEPARIN
AMOUNT....................................................................................92
4.2.3 IN VITRO RELEASE
STUDY..............................................................................................
96
4.3 EX VIVO BUCCAL MUCOSAL PERMEATION AND CONFOCAL MICROSCOPIC STUDIES
............
100
4.4 DEVELOPMENT OF LYOPHILIZED SOLID DOSAGE FORM INCORPORATING AMMONIO
METHACRYLATE COPOLYMER
NANOPARTICLES...............................................................................114
4.4.1 PREPARATION OF LYOPHILIZED POWDER OF AMC NANOPARTICLES
..............................
115
4.4.1.1 LYOPHILIZATION OF UNLOADED AMC NANOPARTICLES
...........................................
115
4.4.1.2 LYOPHILIZATION OF LMWH-LOADED AMC NANOPARTICLES
..................................
118
4.4.2 STABILITY STUDY OF LYOPHILIZED POWDER OF LMWH-LOADED AMC
NANOPARTICLES 121
4.4.3 PREPARATION OF BUCCAL LYOPHILISATE INCORPORATING AMC
NANOPARTICLES.............124
4.4.4 DISSOLUTION TEST OF BUCCAL LYOPHILISATES
...............................................................
127
4.4.5 DISINTEGRATION TIME AND RESIDUAL WATER CONTENT OF BUCCAL
LYOPHILISATES...........129
4.4.6 SEM STUDY OF BUCCAL
LYOPHILISATES.......................................................................131
4.4.7 STABILITY STUDY OF BUCCAL
LYOPHILISATES..................................................................134
5 SUMMARY AND
CONCLUSION...........................................................................136
6 LIST OF
ABBREVIATIONS...................................................................................
144
7
APPENDIX........................................................................................................147
7.1
SUBSTANCES...................................................................................................................147
7.2 SUPPLEMENTARY TABLES AND
FIGURES...........................................................................149
8 LIST OF
FIGURES...............................................................................................
162
9 LIST OF
TABLES................................................................................................
177
10
REFERENCES......................................................................................................180
11 PUBLICATIONS, 203
|
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| physical | VII, 204 Seiten Diagramme, Illustrationen |
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| spelling | Mouftah, Samiha Omar Abduarhman Verfasser (DE-588)1138457930 aut In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin vorgelegt von Samiha Omar Abduarhman Mouftah Bonn 2017 VII, 204 Seiten Diagramme, Illustrationen txt rdacontent n rdamedia nc rdacarrier Dissertation Rheinische Friedrich-Wilhelms Universität Bonn 2017 Methacrylsäurederivate (DE-588)4346931-0 gnd rswk-swf Heparin (DE-588)4024422-2 gnd rswk-swf Nanopartikel (DE-588)4333369-2 gnd rswk-swf Mundhöhle (DE-588)4040731-7 gnd rswk-swf Therapeutisches System (DE-588)4267580-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Heparin (DE-588)4024422-2 s Therapeutisches System (DE-588)4267580-7 s Mundhöhle (DE-588)4040731-7 s Methacrylsäurederivate (DE-588)4346931-0 s Nanopartikel (DE-588)4333369-2 s DE-604 Rheinische Friedrich-Wilhelms-Universität Bonn (DE-588)36150-1 dgg DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029878981&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Mouftah, Samiha Omar Abduarhman In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin Methacrylsäurederivate (DE-588)4346931-0 gnd Heparin (DE-588)4024422-2 gnd Nanopartikel (DE-588)4333369-2 gnd Mundhöhle (DE-588)4040731-7 gnd Therapeutisches System (DE-588)4267580-7 gnd |
| subject_GND | (DE-588)4346931-0 (DE-588)4024422-2 (DE-588)4333369-2 (DE-588)4040731-7 (DE-588)4267580-7 (DE-588)4113937-9 |
| title | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin |
| title_auth | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin |
| title_exact_search | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin |
| title_full | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin vorgelegt von Samiha Omar Abduarhman Mouftah |
| title_fullStr | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin vorgelegt von Samiha Omar Abduarhman Mouftah |
| title_full_unstemmed | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin vorgelegt von Samiha Omar Abduarhman Mouftah |
| title_short | In vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin |
| title_sort | in vitro and ex vivo evaluation of ammonio methacrylate copolymer nanoparticles for buccal delivery of low molecular weight heparin |
| topic | Methacrylsäurederivate (DE-588)4346931-0 gnd Heparin (DE-588)4024422-2 gnd Nanopartikel (DE-588)4333369-2 gnd Mundhöhle (DE-588)4040731-7 gnd Therapeutisches System (DE-588)4267580-7 gnd |
| topic_facet | Methacrylsäurederivate Heparin Nanopartikel Mundhöhle Therapeutisches System Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029878981&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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