Drug nanocrystals prepared by high pressure homogenization: the Universal formulation approach for poorly soluble drugs
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2005
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | V, 197 S. Ill., graph. Darst. |
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| 245 | 1 | 0 | |a Drug nanocrystals prepared by high pressure homogenization |b the Universal formulation approach for poorly soluble drugs |c von Jan Möschwitzer |
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| 502 | |a Berlin, Freie Univ., Diss., 2005 | ||
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| adam_text | DRUG NANOCRYSTALS PREPARED BY HIGH PRESSURE HOMOGENIZATION - THE
UNIVERSAL FORMULATION APPROACH FOR POORLY SOLUBLE DRUGS
INAUGURAL-DISSERTATION ZUR ERLANGUNG DES AKADEMISCHEN GRADES DES DOKTORS
DER NATURWISSENSCHAFTEN (DR. RER. NAT.) EINGEREICHT IM FACHBEREICH
BIOLOGIE, CHEMIE, PHARMAZIE DER FREIEN UNIVERSITAT BERLIN VORGELEGT VON
JAN MOSCHWITZER AUS BERLIN NOVEMBER, 2005 TABLE OF CONTENTS TABLE OF
CONTENTS 1. INTRODUCTION 1 1.1. TECHNOLOGIES FOR THE FORMULATION OF
POORLY SOLUBLE DRUGS 1 1.2. CLASSICAL APPROACHES 3 1.2.1 SALT
FORMATION/PH ADJUSTMENT 4 1.2.2. COSOLVENTS 5 1.2.3. SURFACTANT SYSTEMS
6 1.2.4. LIPID BASED SYSTEMS 6 1.2.5. MICROEMULSIONS 7 1.2.5. LIPOSOMES
AND MIXED MICELLES 7 1.2.6. SOLUBLIZATION BY SOLID-STATE MANIPULATION 8
1.2.7. SOLID DISPERSIONS AND SOLID SOLUTIONS 9 1.2.8 CYCLODEXTRINES 10
1.3. PARTICLE SIZE REDUCTION TECHNIQUES 11 1.3.1. NANOCRYSTALS
TECHNOLOGY (BEAD OR PEARL MILLING) 11 1.3.2. PRECIPITATION METHODS 15
1.3.3. NANOPARTICLES PRODUCED BY HIGH PRESSURE HOMOGENIZATION 16
1.3.3.1. MICROFLUIDIZER TECHNOLOGY (IDD-P* TECHNOLOGY) 16 1.3.3.2.
PISTON-GAP HOMOGENIZATION IN WATER (DISSOCUBES TECHNOLOGY) 17 1.3.3.3.
NANOPURE TECHNOLOGY 19 1.3.4. COMBINATION TECHNOLOGIES 20 1.3.4.1.
NANOEDGE* TECHNOLOGOGY 20 1.3.4.2. NANOPURE XP TECHNOLOGOGY 21 1.3.5
OTHER TECHNIQUES FOR THE PRODUCTION OF DRUG NANOCRYSTALS 23 1.3.5.1.
RAPID EXPANSION OF SUPERCRITICAL SOLUTION (RESS) 23 1.3.5.2. RAPID
EXPANSION FROM SUPERCRITICAL TO AQUEOUS SOLUTION (RESAS) 24 1.3.5.3.
RESSAS TECHNOLOGY 24 1.3.5.4. SOLUTION ENHANCED DISPERSION BY THE
SUPERCRITICAL FLUIDS (SEDS) 24 1.3.5.5. SPRAY FREEZING INTO LIQUID (SFL)
25 1.3.5.6. EVAPORATIVE PRECIPITATION INTO AQUEOUS SOLUTION (EPAS) 25
TABLE OF CONTENTS 1.4. PHYSICO-CHEMICAL PROPERTIES OF DRUG NANOCRYSTALS
26 1.5. POTENTIAL CLINICAL ADVANTAGES OF DRUG NANOCRYSTALS 28 1.5.1.
APPLICATION FOR ORAL DELIVERY 28 1.5.2. PARENTERAL ADMINISTRATION OF
DRUG NANOCRYSTALS 29 1.5.3. DRUG NANOCRYSTALS FOR PULMONARY DRUG
DELIVERY 30 1.5.4. OTHER ADMINISTRATION ROUTES 31 1.6. FINAL
FORMULATIONS FOR DRUG NANOCRYSTALS 31 1.7. CONCLUSION 33 1.8. RESEARCH
OBJECTIVES 34 2. MATERIALS AND METHODS 35 2.1 MATERIALS 35 2.1.1.
OMEPRAZOLE 35 2.1.2. BUDESONIDE 36 2.1.3. HYDROCORTISONE ACETATE 37
2.1.4. IBUPROFEN 38 2.1.5. POLYMERIC STABILIZERS AND SURFACTANTS 39
2.1.6. POLYMERS AND BINDERS 39 2.1.7. OTHER CHEMICALS 39 2.1.8.
COMMERCIAL DRUG PRODUCTS 39 IX METHODS 40 2.2.1. HIGH PRESSURE
HOMOGENIZATION 40 2.2.2. BEAD MILLING 41 2.2.3. LASER DIFFRACTOMETRY
(LD) 41 2.2.4. PHOTON CORRELATION SPECTROSCOPY (PCS) 42 2.2.5. ZETA
POTENTIAL DETERMINATION 42 2.2.6. POLARIZED LIGHT MICROSCOPY 43 2.2.7.
SCANNING ELECTRON MICROSCOPY I (BUDESONIDE FORMULATIONS) 43 2.2.8.
SCANNING ELECTRON MICROSCOPY II (ALL OTHER FORMULATIONS) 43 2.2.9.
ENVIRONMENTAL SCANNING ELECTRON MICROSCOPY (HCA PELLETS) 44 2.2.10. HIGH
PERFORMANCE LIQUID CHROMATOGRAPHY 44 2.2.10.1. OMEPRAZOLE 44 2.2.10.2.
HYDROCORTISONE ACETATE 44 2.2.10.3. BUDESONIDE 45 2.2.11. DIFFERENTIAL
SCANNING CALORIMETRY (DSC) 45 II TABLE OF CONTENTS 2.2.12. X-RAY
DIFFRACTION 45 2.2.13. KARL-FISCHER-TITRATION 46 2.2.14. SPRAY DRYING
(MUCOADHESIVE MICROPARTICLES) 46 2.2.15. SPRAY DRYING (ENTERIC COATED
DRUG NANOCRYSTALS) 46 2.2.16. SPRAY DRYING (MODIFICATION OF THE DRUG
MATERIAL) 47 2.2.17. CHITOSAN BEAD PREPARATION (DROPPING METHOD) 48
2.2.18. PREPARATION OF MATRIX CORES 48 2.2.19. NANOSUSPENSION LAYERING
TECHNIQUE 48 2.2.20. PREPARATION OF DRUG-FREE COLORED PLACEBO CORES 49
2.2.21. FLUIDIZED BED COATING (APPLICATION OF AN ENTERIC TOP-COATING) 49
2.2.22. IN-VITRO DISSOLUTION TESTING 51 2.2.22.1. DRUG RELEASE STUDIES
IN BOTTLES 51 2.2.22.2. DRUG RELEASE STUDIES IN A STANDARD DISSOLUTION
TESTER 51 2.2.23. MUCOADHESION TEST 52 2.2.23.1. PREPARATION OF THE
MUCOADHESION TEST SYSTEM 52 2.2.23.2. MUCOADHESION TEST STUDIES 52
2.2.23.4 STATISTICAL ANALYSIS OF THE MUCOADHESION TEST RESULTS 54 3.
RESULTS AND DISCUSSION 55 3.1. HIGH PRESSURE HOMOGENIZATION FOR CHEMICAL
STABILIZATION 55 3.1.1. STORAGE CONDITIONS 56 3.1.2. INFLUENCE OF
STABILIZER 57 3.1.4. INFLUENCE OF CYCLE NUMBER, DRUG CONTENT AND
DISPERSION MEDIUM 58 3.1.5. PROCESS PARAMETERS - TEMPERATURE 61 3.1.6.
PHYSICAL STABILITY 62 3.1.7. IMPROVEMENT OF CHEMICAL STABILITY 63 3.1.8.
CONCLUSIONS 66 3.2 FINAL DOSAGE FORMS FOR MUCOADHESIVE DRUG NANOCRYSTALS
67 3.2.1. DRUG NANOCRYSTALS LOADED MATRIX PELLETS 67 3.2.1.1. PRINCIPLE
OF ACTION . . 69 3.2.1.2. PROCESS DEVELOPMENT 70 3.2.1.3. FORMULATION
SCREENING 71 3.2.1.4. BUDESONIDE NANOSUSPENSIONS 74 3.2.1.4. BUDESONIDE
NANOSUSPENSIONS 74 3.2.1.5. PELLET PREPARATION AND PELLET MORPHOLOGY 78
III TABLE OF CONTENTS 3.2.1.6. REDISPERSIBILITY OF DRUG NANOCRYSTALS
FROM PELLET FORMULATION 80 3.2.1.7. DRUG RELEASE STUDIES 81 3.2.1.8.
CONCLUSION 84 3.2.2. PH-SENSITIVE CHITOSAN BEADS 85 3.2.2.1. PROCESS
DEVELOPMENT 86 3.2.2.2. PREPARATION OF THE NANOSUSPENSION 86 3.2.2.3.
BEAD PREPARATION 88 3.2.2.4. DRUG RELEASE OF CHITOSAN BEADS 89 3.2.2.5.
CONCLUSION 89 3.2.3. NANOSUSPENSION LAYERING 90 3.2.3.1. PROCESS
DEVELOPMENT 92 3.2.3.2. NANOSUSPENSION PREPARATION AND SIZE MEASUREMENT
RESULTS 93 3.2.3.3. X-RAY STUDIES 96 3.2.3.4. PELLET PREPARATION AND
MORPHOLOGY 98 3.2.3.5. IN VITRO DISSOLUTION PROFILE 100 3.2.3.6.
CONCLUSIONS 102 3.2.4. FACTORS INFLUENCING THE RELEASE KINETIC OF
PELLETS 103 3.2.4.1. FORMULATION SCREENING OF THE LAYERING DISPERSIONS
104 3.2 4.2. PRODUCTION TECHNIQUES 107 3.2.4.3. INFLUENCE OF BINDER TYPE
ON THE DRUG RELEASE 108 3.2.4.4. INFLUENCE OF DRUG LOADING 109 3.2.4.5.
INFLUENCE OF CORE MATERIAL ILL 3.2.4.6. CONCLUSION 113 3.2.5. DRUG
NANOCRYSTALS LOADED CHITOSAN MICROPARICLES 114 3.2.5.1. PROCESS
DEVELOPMENT 116 3.2.5.2. PRODUCTION OF MUCOADHESIVE NANOSUSPENSIONS 117
3.2.6. * ENTERIC COATED DRUG NANOCRYSTALS FOR CONTROLLED DRUG RELEASE
128 3.2.6.1. DESCRIPTION OF THE PROCESS 129 3.2.6.2. ENTERIC COATED DRUG
NANOCRYSTALS OF HCA AND OMEPRAZOLE 130 3.2.6.3. CONCLUSION 132 IV TABLE
OF CONTENTS 3.3. NEW EFFECTIVE HOMOGENIZATION METHOD H42 133 3.3.1.
HYDROCORTISONE ACETATE PROCESSED WITH H42 136 3.3.1.1. CHARACTERIZATION
OF THE DIFFERENT DRUG POWDERS 136 3.3.1.2. NANOSUSPENSION PREPARATION
AND CHARACTERIZATION 139 3.3.1.3. SOLUBILITY ENHANCEMENT 147 3.3.1.4.
PHYSICAL LONG-TERM STABILITY 148 3.3.1.5. CONCLUSION 150 3.3.2.
IBUPROFEN PROCESSED WITH H42 151 3.3.2.1. PRODUCTION AND
CHARACTERIZATION OF IBUPROFEN POWDERS 151 3.3.2.2. INFLUENCE OF H42 ON
THE DIMINUTION EFFECTIVENESS OF IBUPROFEN 153 3.3.2.3. CONCLUSION 157
3.3.3. COMPARISON OF MILLING, HPH, AND H42 158 3.3.3.1. MINIMAL
ACHIEVABLE PARTICLE SIZE 158 3.3.3.2. STABILITY UPON LONG-TERM STORAGE
163 3.3.2.3. CONCLUSION 165 4. SUMMARV 167 5. ZUSAMMENFASSUNG 173 6.
REFERENCES 181 LIST OF PUBLICATIONS 193 ACKNOWLEDGEMENTS 196 CURRICULUM
VITAE 197
|
| adam_txt |
DRUG NANOCRYSTALS PREPARED BY HIGH PRESSURE HOMOGENIZATION - THE
UNIVERSAL FORMULATION APPROACH FOR POORLY SOLUBLE DRUGS
INAUGURAL-DISSERTATION ZUR ERLANGUNG DES AKADEMISCHEN GRADES DES DOKTORS
DER NATURWISSENSCHAFTEN (DR. RER. NAT.) EINGEREICHT IM FACHBEREICH
BIOLOGIE, CHEMIE, PHARMAZIE DER FREIEN UNIVERSITAT BERLIN VORGELEGT VON
JAN MOSCHWITZER AUS BERLIN NOVEMBER, 2005 TABLE OF CONTENTS TABLE OF
CONTENTS 1. INTRODUCTION 1 1.1. TECHNOLOGIES FOR THE FORMULATION OF
POORLY SOLUBLE DRUGS 1 1.2. CLASSICAL APPROACHES 3 1.2.1 SALT
FORMATION/PH ADJUSTMENT 4 1.2.2. COSOLVENTS 5 1.2.3. SURFACTANT SYSTEMS
6 1.2.4. LIPID BASED SYSTEMS 6 1.2.5. MICROEMULSIONS 7 1.2.5. LIPOSOMES
AND MIXED MICELLES 7 1.2.6. SOLUBLIZATION BY SOLID-STATE MANIPULATION 8
1.2.7. SOLID DISPERSIONS AND SOLID SOLUTIONS 9 1.2.8 CYCLODEXTRINES 10
1.3. PARTICLE SIZE REDUCTION TECHNIQUES 11 1.3.1. NANOCRYSTALS
TECHNOLOGY (BEAD OR PEARL MILLING) 11 1.3.2. PRECIPITATION METHODS 15
1.3.3. NANOPARTICLES PRODUCED BY HIGH PRESSURE HOMOGENIZATION 16
1.3.3.1. MICROFLUIDIZER TECHNOLOGY (IDD-P* TECHNOLOGY) 16 1.3.3.2.
PISTON-GAP HOMOGENIZATION IN WATER (DISSOCUBES TECHNOLOGY) 17 1.3.3.3.
NANOPURE TECHNOLOGY 19 1.3.4. COMBINATION TECHNOLOGIES 20 1.3.4.1.
NANOEDGE* TECHNOLOGOGY 20 1.3.4.2. NANOPURE XP TECHNOLOGOGY 21 1.3.5
OTHER TECHNIQUES FOR THE PRODUCTION OF DRUG NANOCRYSTALS 23 1.3.5.1.
RAPID EXPANSION OF SUPERCRITICAL SOLUTION (RESS) 23 1.3.5.2. RAPID
EXPANSION FROM SUPERCRITICAL TO AQUEOUS SOLUTION (RESAS) 24 1.3.5.3.
RESSAS TECHNOLOGY 24 1.3.5.4. SOLUTION ENHANCED DISPERSION BY THE
SUPERCRITICAL FLUIDS (SEDS) 24 1.3.5.5. SPRAY FREEZING INTO LIQUID (SFL)
25 1.3.5.6. EVAPORATIVE PRECIPITATION INTO AQUEOUS SOLUTION (EPAS) 25
TABLE OF CONTENTS 1.4. PHYSICO-CHEMICAL PROPERTIES OF DRUG NANOCRYSTALS
26 1.5. POTENTIAL CLINICAL ADVANTAGES OF DRUG NANOCRYSTALS 28 1.5.1.
APPLICATION FOR ORAL DELIVERY 28 1.5.2. PARENTERAL ADMINISTRATION OF
DRUG NANOCRYSTALS 29 1.5.3. DRUG NANOCRYSTALS FOR PULMONARY DRUG
DELIVERY 30 1.5.4. OTHER ADMINISTRATION ROUTES 31 1.6. FINAL
FORMULATIONS FOR DRUG NANOCRYSTALS 31 1.7. CONCLUSION 33 1.8. RESEARCH
OBJECTIVES 34 2. MATERIALS AND METHODS 35 2.1 MATERIALS 35 2.1.1.
OMEPRAZOLE 35 2.1.2. BUDESONIDE 36 2.1.3. HYDROCORTISONE ACETATE 37
2.1.4. IBUPROFEN 38 2.1.5. POLYMERIC STABILIZERS AND SURFACTANTS 39
2.1.6. POLYMERS AND BINDERS 39 2.1.7. OTHER CHEMICALS 39 2.1.8.
COMMERCIAL DRUG PRODUCTS 39 IX METHODS 40 2.2.1. HIGH PRESSURE
HOMOGENIZATION 40 2.2.2. BEAD MILLING 41 2.2.3. LASER DIFFRACTOMETRY
(LD) 41 2.2.4. PHOTON CORRELATION SPECTROSCOPY (PCS) 42 2.2.5. ZETA
POTENTIAL DETERMINATION 42 2.2.6. POLARIZED LIGHT MICROSCOPY 43 2.2.7."
SCANNING ELECTRON MICROSCOPY I (BUDESONIDE FORMULATIONS) 43 2.2.8.
SCANNING ELECTRON MICROSCOPY II (ALL OTHER FORMULATIONS) 43 2.2.9.
ENVIRONMENTAL SCANNING ELECTRON MICROSCOPY (HCA PELLETS) 44 2.2.10. HIGH
PERFORMANCE LIQUID CHROMATOGRAPHY 44 2.2.10.1. OMEPRAZOLE 44 2.2.10.2.
HYDROCORTISONE ACETATE 44 2.2.10.3. BUDESONIDE 45 2.2.11. DIFFERENTIAL
SCANNING CALORIMETRY (DSC) 45 II TABLE OF CONTENTS 2.2.12. X-RAY
DIFFRACTION 45 2.2.13. KARL-FISCHER-TITRATION 46 2.2.14. SPRAY DRYING
(MUCOADHESIVE MICROPARTICLES) 46 2.2.15. SPRAY DRYING (ENTERIC COATED
DRUG NANOCRYSTALS) 46 2.2.16. SPRAY DRYING (MODIFICATION OF THE DRUG
MATERIAL) 47 2.2.17. CHITOSAN BEAD PREPARATION (DROPPING METHOD) 48
2.2.18. PREPARATION OF MATRIX CORES 48 2.2.19. NANOSUSPENSION LAYERING
TECHNIQUE 48 2.2.20. PREPARATION OF DRUG-FREE COLORED PLACEBO CORES 49
2.2.21. FLUIDIZED BED COATING (APPLICATION OF AN ENTERIC TOP-COATING) 49
2.2.22. IN-VITRO DISSOLUTION TESTING 51 2.2.22.1. DRUG RELEASE STUDIES
IN BOTTLES 51 2.2.22.2. DRUG RELEASE STUDIES IN A STANDARD DISSOLUTION
TESTER 51 2.2.23. MUCOADHESION TEST 52 2.2.23.1. PREPARATION OF THE
MUCOADHESION TEST SYSTEM 52 2.2.23.2. MUCOADHESION TEST STUDIES 52
2.2.23.4 STATISTICAL ANALYSIS OF THE MUCOADHESION TEST RESULTS 54 3.
RESULTS AND DISCUSSION 55 3.1. HIGH PRESSURE HOMOGENIZATION FOR CHEMICAL
STABILIZATION 55 3.1.1. STORAGE CONDITIONS 56 3.1.2. INFLUENCE OF
STABILIZER 57 3.1.4. INFLUENCE OF CYCLE NUMBER, DRUG CONTENT AND
DISPERSION MEDIUM 58 3.1.5. PROCESS PARAMETERS - TEMPERATURE 61 3.1.6.
PHYSICAL STABILITY 62 3.1.7. IMPROVEMENT OF CHEMICAL STABILITY 63 3.1.8.
CONCLUSIONS 66 3.2 FINAL DOSAGE FORMS FOR MUCOADHESIVE DRUG NANOCRYSTALS
67 3.2.1. DRUG NANOCRYSTALS LOADED MATRIX PELLETS 67 3.2.1.1. PRINCIPLE
OF ACTION .'. 69 3.2.1.2. PROCESS DEVELOPMENT 70 3.2.1.3. FORMULATION
SCREENING 71 3.2.1.4. BUDESONIDE NANOSUSPENSIONS 74 3.2.1.4. BUDESONIDE
NANOSUSPENSIONS 74 3.2.1.5. PELLET PREPARATION AND PELLET MORPHOLOGY 78
III TABLE OF CONTENTS 3.2.1.6. REDISPERSIBILITY OF DRUG NANOCRYSTALS
FROM PELLET FORMULATION 80 3.2.1.7. DRUG RELEASE STUDIES 81 3.2.1.8.
CONCLUSION 84 3.2.2. PH-SENSITIVE CHITOSAN BEADS 85 3.2.2.1. PROCESS
DEVELOPMENT 86 3.2.2.2. PREPARATION OF THE NANOSUSPENSION 86 3.2.2.3.
BEAD PREPARATION 88 3.2.2.4. DRUG RELEASE OF CHITOSAN BEADS 89 3.2.2.5.
CONCLUSION 89 3.2.3. NANOSUSPENSION LAYERING 90 3.2.3.1. PROCESS
DEVELOPMENT 92 3.2.3.2. NANOSUSPENSION PREPARATION AND SIZE MEASUREMENT
RESULTS 93 3.2.3.3. X-RAY STUDIES 96 3.2.3.4. PELLET PREPARATION AND
MORPHOLOGY 98 3.2.3.5. IN VITRO DISSOLUTION PROFILE 100 3.2.3.6.
CONCLUSIONS 102 3.2.4. FACTORS INFLUENCING THE RELEASE KINETIC OF
PELLETS 103 3.2.4.1. FORMULATION SCREENING OF THE LAYERING DISPERSIONS
104 3.2 4.2. PRODUCTION TECHNIQUES 107 3.2.4.3. INFLUENCE OF BINDER TYPE
ON THE DRUG RELEASE 108 3.2.4.4. INFLUENCE OF DRUG LOADING 109 3.2.4.5.
INFLUENCE OF CORE MATERIAL ILL 3.2.4.6. CONCLUSION 113 3.2.5. DRUG
NANOCRYSTALS LOADED CHITOSAN MICROPARICLES 114 3.2.5.1. PROCESS
DEVELOPMENT 116 3.2.5.2. PRODUCTION OF MUCOADHESIVE NANOSUSPENSIONS 117
3.2.6. * ENTERIC COATED DRUG NANOCRYSTALS FOR CONTROLLED DRUG RELEASE
128 3.2.6.1. DESCRIPTION OF THE PROCESS 129 3.2.6.2. ENTERIC COATED DRUG
NANOCRYSTALS OF HCA AND OMEPRAZOLE 130 3.2.6.3. CONCLUSION 132 IV TABLE
OF CONTENTS 3.3. NEW EFFECTIVE HOMOGENIZATION METHOD H42 133 3.3.1.
HYDROCORTISONE ACETATE PROCESSED WITH H42 136 3.3.1.1. CHARACTERIZATION
OF THE DIFFERENT DRUG POWDERS 136 3.3.1.2. NANOSUSPENSION PREPARATION
AND CHARACTERIZATION 139 3.3.1.3. SOLUBILITY ENHANCEMENT 147 3.3.1.4.
PHYSICAL LONG-TERM STABILITY 148 3.3.1.5. CONCLUSION 150 3.3.2.
IBUPROFEN PROCESSED WITH H42 151 3.3.2.1. PRODUCTION AND
CHARACTERIZATION OF IBUPROFEN POWDERS 151 3.3.2.2. INFLUENCE OF H42 ON
THE DIMINUTION EFFECTIVENESS OF IBUPROFEN 153 3.3.2.3. CONCLUSION 157
3.3.3. COMPARISON OF MILLING, HPH, AND H42 158 3.3.3.1. MINIMAL
ACHIEVABLE PARTICLE SIZE 158 3.3.3.2. STABILITY UPON LONG-TERM STORAGE
163 3.3.2.3. CONCLUSION 165 4. SUMMARV 167 5. ZUSAMMENFASSUNG 173 6.
REFERENCES 181 LIST OF PUBLICATIONS 193 ACKNOWLEDGEMENTS 196 CURRICULUM
VITAE 197 |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Möschwitzer, Jan 1974- |
| author_GND | (DE-588)131714090 |
| author_facet | Möschwitzer, Jan 1974- |
| author_role | aut |
| author_sort | Möschwitzer, Jan 1974- |
| author_variant | j m jm |
| building | Verbundindex |
| bvnumber | BV021499386 |
| ctrlnum | (OCoLC)162212836 (DE-599)BVBBV021499386 |
| dewey-full | 615.19 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 615 - Pharmacology and therapeutics |
| dewey-raw | 615.19 |
| dewey-search | 615.19 |
| dewey-sort | 3615.19 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV021499386 |
| illustrated | Illustrated |
| index_date | 2024-07-02T14:14:57Z |
| indexdate | 2024-07-09T20:37:11Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-014716134 |
| oclc_num | 162212836 |
| open_access_boolean | |
| owner | DE-29T DE-12 DE-355 DE-BY-UBR DE-83 DE-188 |
| owner_facet | DE-29T DE-12 DE-355 DE-BY-UBR DE-83 DE-188 |
| physical | V, 197 S. Ill., graph. Darst. |
| publishDate | 2005 |
| publishDateSearch | 2005 |
| publishDateSort | 2005 |
| record_format | marc |
| spelling | Möschwitzer, Jan 1974- Verfasser (DE-588)131714090 aut Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs von Jan Möschwitzer 2005 V, 197 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Berlin, Freie Univ., Diss., 2005 Arzneimittel (DE-588)4003115-9 gnd rswk-swf Hochdruckhomogenisation (DE-588)4138005-8 gnd rswk-swf Nanostrukturiertes Material (DE-588)4342626-8 gnd rswk-swf Schwerlöslicher Stoff (DE-588)4352869-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Arzneimittel (DE-588)4003115-9 s Schwerlöslicher Stoff (DE-588)4352869-7 s Hochdruckhomogenisation (DE-588)4138005-8 s Nanostrukturiertes Material (DE-588)4342626-8 s DE-188 GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014716134&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Möschwitzer, Jan 1974- Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs Arzneimittel (DE-588)4003115-9 gnd Hochdruckhomogenisation (DE-588)4138005-8 gnd Nanostrukturiertes Material (DE-588)4342626-8 gnd Schwerlöslicher Stoff (DE-588)4352869-7 gnd |
| subject_GND | (DE-588)4003115-9 (DE-588)4138005-8 (DE-588)4342626-8 (DE-588)4352869-7 (DE-588)4113937-9 |
| title | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs |
| title_auth | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs |
| title_exact_search | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs |
| title_exact_search_txtP | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs |
| title_full | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs von Jan Möschwitzer |
| title_fullStr | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs von Jan Möschwitzer |
| title_full_unstemmed | Drug nanocrystals prepared by high pressure homogenization the Universal formulation approach for poorly soluble drugs von Jan Möschwitzer |
| title_short | Drug nanocrystals prepared by high pressure homogenization |
| title_sort | drug nanocrystals prepared by high pressure homogenization the universal formulation approach for poorly soluble drugs |
| title_sub | the Universal formulation approach for poorly soluble drugs |
| topic | Arzneimittel (DE-588)4003115-9 gnd Hochdruckhomogenisation (DE-588)4138005-8 gnd Nanostrukturiertes Material (DE-588)4342626-8 gnd Schwerlöslicher Stoff (DE-588)4352869-7 gnd |
| topic_facet | Arzneimittel Hochdruckhomogenisation Nanostrukturiertes Material Schwerlöslicher Stoff Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014716134&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT moschwitzerjan drugnanocrystalspreparedbyhighpressurehomogenizationtheuniversalformulationapproachforpoorlysolubledrugs |