Pharmaceutical dosage forms and drug delivery:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Boca Raton, FL
CRC Press
2007
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| Schriftenreihe: | CRC Press pharmacy education series
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Includes bibliographical references and index |
| Beschreibung: | XXXI, 300 S. graph. Darst. |
| ISBN: | 9780849392856 0849392853 |
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| 650 | 4 | |a Médicaments - Administration - Dispositifs | |
| 650 | 4 | |a Médicaments - Formes pharmaceutiques | |
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| adam_text | PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY RAM I. MAHATO CRC PRESS
TAYLOR & FRANCIS GROUP BOCA RATON LONDON NEWYORV CRC PRESS IS AN IMPRINT
OF THE TAYLOR & FRANCIS GROUP, AN INFORMA BUSINESS TABLE OF CONTENTS
LIST OF ILLUSTRATIONS XIX LIST OF TABLES XXIII FOREWORD XXV PREFACE
XXVII ACKNOWLEDGMENTS XXIX ABOUT THE AUTHOR XXXI CHAPTER 1 DRUG
DEVELOPMENT AND REGULATORY PROCESS 1 LEARNING OBJECTIVES 1 I.
INTRODUCTION 1 II. IDENTIFICATION OF NEW THERAPEUTIC MOLECULES 2 A.
EXTRACTION FROM PLANTS 2 B. ORGANIC SYNTHESIS 3 C. USE OF ANIMALS 4 D.
GENETIC ENGINEERING 4 E. GENE THERAPY 4 III. PRECLINICAL RESEARCH 4 IV.
FORMULATION DEVELOPMENT 5 V. REGULATORY ISSUES 5 A. INVESTIGATIONAL NEW
DRUG (IND) APPLICATION 5 B. CLINICAL TRIALS 6 1. PHASE I CLINICAL TRIALS
6 2. PHASE II CLINICAL TRIALS 6 3. PHASE III CLINICAL TRIALS 7 C. NEW
DRUG APPLICATION (NDA) 7 D. APPROVAL AND POSTMARKETING SURVEILLANCE 7 E.
ABBREVIATED NEW DRUG APPLICATION (ANDA) 8 F. ROLE OF FDA S ADVISORY
COMMITTEES 8 REVIEW QUESTIONS 8 BIBLIOGRAPHY 9 CHAPTER 2 PHARMACEUTICAL
AND FORMULATION CONSIDERATIONS 11 LEARNING OBJECTIVES 11 I. INTRODUCTION
11 II. ADVANTAGES OF PHARMACEUTICAL DOSAGE FORMS 11 VIII PHARMACEUTICAL
DOSAGE FORMS AND DRUG DELIVERY III. INFLUENTIAL FACTORS IN DOSAGE FORM
DESIGN 12 A. MOLECULAR SIZE AND VOLUME 13 B. DRUG SOLUBILITY AND PH 14
C. LIPOPHILICITY AND PARTITION COEFFICIENT 16 D. POLYMORPHISM 17 E.
STABILITY 19 F. PKA/DISSOCIATION CONSTANTS 20 G. DEGREE OF LONIZATION
AND PH-PARTITION THEORY 24 1. LIMITATIONS OF PH-PARTITION THEORY 24
REVIEW QUESTIONS 25 BIBLIOGRAPHY 26 CHAPTER 3 BIOPHARMACEUTICAL AND
PHYSIOLOGICAL CONSIDERATIONS 29 LEARNING OBJECTIVES 29 I. INTRODUCTION
29 II. DRUG TRANSPORT ACROSS A POLYMERIC BARRIER 30 III. FICK S LAWS OF
DIFFUSION 30 A. FICK S FIRST LAW OF DIFFUSION 30 B. FICK S SECOND LAW OF
DIFFUSION 32 1. STEADY-STATE CONDITIONS 32 2. LAG TIME 34 IV. PORE
DIFFUSION 34 V. MATRIX (MONOLITHIC)-TYPE NONDEGRADABLE DEVICE 35 VI.
BIOLOGICAL MEMBRANES AND DRUG ABSORPTION 36 A. PASSIVE TRANSPORT 37 1.
SIMPLE DIFFUSION 37 2. CARRIER-MEDIATED TRANSPORT 37 3. CHANNEL-MEDIATED
TRANSPORT 37 B. ACTIVE TRANSPORT 37 VII. FICK S LAW OF DIFFUSION AND
DRUG ABSORPTION 38 VIII. DISSOLUTION RATE AND NOYES-WHITNEY EQUATION OF
DISSOLUTION 40 IX. FACTORS INFLUENCING DISSOLUTION RATE 41 A.
PHYSICOCHEMICAL PROPERTIES 41 B. THICKNESS OF DIFFUSION LAYER 42 C.
GASTROINTESTINAL FLUIDS 42 D. PARTICLE SIZE 42 E. CRYSTALLINITY 42 F.
POROSITY AND TORTUOSITY OF SOLID PARTICLES 43 G. TEMPERATURE 43 H.
SURFACTANTS 43 X. DRUG ABSORPTION AND BIOAVAILABILITY 43 REVIEW
QUESTIONS 43 BIBLIOGRAPHY 45 TABLE OF CONTENTS CHAPTER 4 COMPLEXATION
AND PROTEIN BINDING 47 LEARNING OBJECTIVES 47 I. INTRODUCTION 47 II.
TYPES OF COMPLEXATION 47 A. COORDINATION COMPLEXES 48 B. MOLECULAR
COMPLEXES 48 C. DRUG COMPLEXES 50 D. POLYMER COMPLEXES 50 E. INCLUSION
COMPLEXES 50 III. DRUG INTERACTION WITH PLASMA PROTEINS 52 IV. BINDING
EQUILIBRIA 52 A. PROTEIN BINDING 54 V. IMPACT OF PLASMA PROTEIN BINDING
ON DOSING REGIMENS 55 REVIEW QUESTIONS 56 BIBLIOGRAPHY 57 CHAPTER 5
CHEMICAL KINETICS AND STABILITY 59 LEARNING OBJECTIVES 59 I.
INTRODUCTION 59 II. RATES AND ORDER OF REACTION 59 A. ZERO-ORDER
REACTIONS 60 B. FIRST-ORDER REACTIONS 61 C. SECOND-ORDER KINETICS 63
III. FACTORS AFFECTING REACTION KINETICS 65 A. CATALYSIS 65 B. EFFECT OF
TEMPERATURE 65 C. EFFECT OF SOLVENT 67 D. EFFECT OF PH 67 E. PRESENCE OF
ADDITIVES 67 IV. PATHWAYS AND PREVENTION OF CHEMICAL DECOMPOSITION OF
DRUGS 68 A. HYDROLYSIS 68 1. CONTROL OF DRUG HYDROLYSIS 69 B. OXIDATION
70 1. CONTROL OF DRUG OXIDATION 72 C. PHOTOLYSIS 72 1. CONTROL OF
PHOTODEGRADATION OF DRUGS 72 REVIEW QUESTIONS 73 BIBLIOGRAPHY 73 CHAPTER
6 INTERFACIAL PHENOMENA 75 LEARNING OBJECTIVES 75 I- INTRODUCTION 75 X
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY II. LIQUID INTERFACES 75
A. SURFACE AND INTERFACIAL TENSIONS 75 B. SURFACE FREE ENERGY 76 III.
ADSORPTION AT SOLID-GAS INTERFACES 77 A. PHYSICAL ADSORPTION 77 B.
CHEMICAL ADSORPTION 78 C. ADSORPTION ISOTHERMS 78 1. FREUNDLICH
ADSORPTION ISOTHERM 78 2. LANGMUIR ADSORPTION ISOTHERM 79 3. BET
ADSORPTION ISOTHERM 80 4. TYPE OF ISOTHERMS 80 IV. ADSORPTION AT
SOLID-LIQUID INTERFACE 81 A. FACTORS AFFECTING ADSORPTION FROM SOLUTION
81 B. APPLICATION OF ADSORPTION 82 V. WETTABILITY AND WETTING AGENTS 83
A. WETTING AGENTS 83 VI. PROTEIN ADSORPTION 84 REVIEW QUESTIONS 84
BIBLIOGRAPHY 85 CHAPTER 7 RHEOLOGY 87 LEARNING OBJECTIVES 87 I.
INTRODUCTION 87 II. NEWTONIAN FLOW 87 A. TEMPERATURE DEPENDENCE AND
VISCOSITY OF LIQUIDS 88 III. NON-NEWTONIAN FLOW 88 A. PLASTIC FLOW 88 B.
PSEUDOPLASTIC FLOW 90 C. DILATANTFLOW 90 IV. THIXOTROPY 91 A. HYSTERESIS
LOOP 91 B. NEGATIVE THIXOTROPY 93 V. PHARMACEUTICAL APPLICATIONS OF
RHEOLOGY 93 REVIEW QUESTIONS 94 BIBLIOGRAPHY 94 CHAPTER 8 DISPERSE
SYSTEM BASICS 95 LEARNING OBJECTIVES 95 I. INTRODUCTION 95 II. TYPES OF
COLLOIDAL SYSTEMS 96 A. LYOPHILIC COLLOIDS 96 B. LYOPHOBIC COLLOIDS 96
C. ASSOCIATION COLLOIDS 97 TABLE OF CONTENTS XI III. KINETIC PROPERTIES
OF COLLOIDS 97 A. BROWNIAN MOVEMENT 97 1. DIFFUSION 96 2. SEDIMENTATION
96 IV. ELECTRICAL PROPERTIES 99 A. IONIZATION 99 B. ION ADSORPTION 100
C. ION DISSOLUTION 100 V. ELECTROSTATIC EFFECT 100 VI. ELECTRICAL DOUBLE
LAYER 100 A. NERST AND ZETA POTENTIALS 102 B. DLVO THEORY 102 C.
ELECTROPHORETIC PHENOMENA 102 VII. STABILITY OF COLLOIDS 103 A.
AGGREGATION 104 B. COAGULATION 104 C. FLOCCULATION 104 REVIEW QUESTIONS
104 BIBLIOGRAPHY 105 CHAPTER 9 SURFACTANTS AND MICELLES 107 LEARNING
OBJECTIVES 107 I. INTRODUCTION 107 II. SURFACTANTS 107 A. TYPES OF
SURFACTANTS 108 1. ANIONIC SURFACTANTS 108 2. CATIONIC SURFACTANTS 109
3. NONIONIC SURFACTANTS 109 4. AMPHOLYTIC SURFACTANTS 109 III. HLB
SYSTEMS 110 IV MICELLES 111 A. TYPES OF MICELLES 114 B. CMC AND MICELLAR
SIZE 114 V. MICELLAR SOLUBILIZATION 115 A. FACTORS AFFECTING
SOLUBILIZATION 115 1. NATURE OF SURFACTANTS 115 2. NATURE OF
SOLUBILIZATES 116 3. EFFECT OF TEMPERATURE 116 4. EFFECT OF PH 116 B.
PHARMACEUTICAL APPLICATIONS OF MICELLAR SOLUBILIZATION 116 C.
THERMODYNAMICS OF SOLUBILIZATION 117 VI. KRAFFT POINT 118 VII. CLOUD
POINT 119 XII PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY REVIEW
QUESTIONS 119 BIBLIOGRAPHY 120 CHAPTER 10 PHARMACEUTICAL SUSPENSIONS 123
LEARNING OBJECTIVES 123 I. INTRODUCTION 123 II. CLASSIFICATION OF
SUSPENSIONS 123 III. CHARACTERISTICS OF PHARMACEUTICAL SUSPENSIONS 124
IV. FORMULATION OF SUSPENSIONS 125 V. FLOCCULATION AND DEFLOCCULATION
126 A. PROPERTIES OF DEFLOCCULATED (DISPERSED) PARTICLES 129 B.
PROPERTIES OF FLOCCULATED PARTICLES 129 VI. SUSPENSION STABILITY 130 A.
ADHESION OF SUSPENSION PARTICLES TO CONTAINERS 130 B. SEDIMENTATION
PARAMETERS 130 C. SEDIMENTATION AND STOKE S LAW 131 REVIEW QUESTIONS 132
BIBLIOGRAPHY 133 CHAPTER 11 PHARMACEUTICAL EMULSIONS 135 LEARNING
OBJECTIVES 135 I. INTRODUCTION 135 II. ADVANTAGES OF EMULSION DOSAGE
FORMS 135 III. TYPES OF EMULSIONS 135 A. OIL-IN-WATER EMULSIONS 136 B.
WATER-IN-OIL EMULSIONS 136 C. MULTIPLE EMULSIONS 137 D. MICROEMULSIONS
137 IV. ROLES OF INTERFACIAL FREE ENERGY ON EMULSIFICATION 137 V.
FORMULATIONS OF EMULSIONS 138 VI. EMULSIFYING AGENTS 138 A. SURFACTANTS
140 B. HYDROPHILIC COLLOIDS 140 C. FINELY DIVIDED SOLID PARTICLES 141
VII. TYPES OF INSTABILITY IN EMULSIONS 141 A. CREAMING AND SEDIMENTATION
141 B. BREAKING AND COALESCENCE 142 C. PHASE INVERSION 143 D. MICROBIAL
GROWTH 143 REVIEW QUESTIONS 143 BIBLIOGRAPHY 144 TABLE OF CONTENTS
CHAPTER 12 PHARMACEUTICAL SOLUTIONS 145 LEARNING OBJECTIVES 145 I.
INTRODUCTION 145 II. PH AND SOLUBILITY 146 III. BUFFER AND BUFFER
CAPACITY 146 IV. VEHICLES 148 V. TYPES OF SOLUTIONS 148 A. SYRUPS 148 B.
ELIXIRS 149 C. TINCTURES 149 D. MISCELLANEOUS SOLUTIONS 149 VI. DRY OR
LYOPHILIZED MIXTURES FOR SOLUTION 150 REVIEW QUESTIONS 150 BIBLIOGRAPHY
150 CHAPTER 13 TABLETS 153 LEARNING OBJECTIVES 153 I. INTRODUCTION 153
II. TYPES OF TABLETS 153 A. SWALLOWABLE TABLETS 153 B. EFFERVESCENT
TABLETS 154 C. CHEWABLE TABLETS 154 D. BUCCAL AND SUBLINGUAL TABLETS 154
E. LOZENGES 154 F. COATED TABLETS 154 G. CONTROLLED-RELEASE TABLETS 155
H. IMMEDIATE-RELEASE TABLETS 156 III. TABLET FORMULATION 156 A. DILUENTS
156 B. ADSORBENTS 157 C. MOISTENING AGENTS 157 D. BINDING AGENTS 157 E.
GLIDANTS 158 F. LUBRICANTS 158 G. DISINTEGRANTS 158 H. MISCELLANEOUS 159
IV POWDER FLOW AND COMPRESSIBILITY 159 V. MANUFACTURING OF TABLETS 159
VI. RELATIONSHIP AMONG DISINTEGRATION. DISSOLUTION, AND ABSORPTION 160
VII. EVALUATION OF TABLETS 161 REVIEW QUESTIONS 161 BIBLIOGRAPHY 163 XIV
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY CHAPTER 14 CAPSULES 165
LEARNING OBJECTIVES 165 I. INTRODUCTION 165 II. HARD GELATIN CAPSULES
166 A. ADVANTAGES AND DISADVANTAGES OF HARD GELATIN CAPSULES 166 B.
FORMULATION OF HARD GELATIN CAPSULES 167 III. SOFT GELATIN CAPSULES 168
A. FORMULATION OF SOFT GELATIN CAPSULES 169 IV. EVALUATION OF CAPSULES
170 REVIEW QUESTIONS 171 BIBLIOGRAPHY 171 CHAPTER 15 INJECTABLE DOSAGE
FORMS 173 LEARNING OBJECTIVES 173 I. INTRODUCTION 173 II. ISOTONICITY
174 III. PARENTERAL ROUTES OF ADMINISTRATION 174 A. INTRAVENOUS ROUTE
174 B. INTRAMUSCULAR ROUTE 175 C. SUBCUTANEOUS ROUTE 175 D. OTHER ROUTES
175 IV. FORMULATION OF PARENTERAL PRODUCTS 176 A. PHYSICOCHEMICAL
PROPERTIES OF THE DRUG 176 B. EXCIPIENTS IN PARENTERAL FORMULATIONS 176
C. VEHICLES 177 V. STERILIZATION OF PARENTERAL PRODUCTS 177 A.
FILTRATION 177 B. DRY HEAT STERILIZATION 178 C. STEAM STERILIZATION 178
D. RADIATION STERILIZATION 178 VI. TYPES OF PARENTERAL DOSAGE FORMS 178
A. SOLUTIONS 178 B. SUSPENSIONS 179 C. EMULSIONS 179 D. DRY POWDERS 179
VII. EVALUATION OF INJECTABLE PRODUCTS 179 A. STERILITY 180 B. PYROGENS
180 C. PANICULATE MATTERS 180 REVIEW QUESTIONS 181 BIBLIOGRAPHY 181
TABLE OF CONTENTS XV CHAPTER 16 SEMISOLID DOSAGE FORMS 183 LEARNING
OBJECTIVES 183 I. INTRODUCTION 183 II. OINTMENTS 183 A. TYPES OF
OINTMENT BASES 183 1. HYDROCARBON BASES 184 2. ABSORPTION BASES 184 3.
EMULSION BASES 184 4. WATER-SOLUBLE BASES 185 B. INCORPORATION OF DRUGS
INTO OINTMENT 185 III. CREAMS 185 IV GELS 186 V LOTIONS 187 VI. PASTES
187 REVIEW QUESTIONS 187 BIBLIOGRAPHY 188 CHAPTER 17 INSERTS, IMPLANTS,
AND DEVICES 189 LEARNING OBJECTIVES 189 I. INTRODUCTION 189 II. INSERTS
189 III. IMPLANTS 191 IV. SUPPOSITORIES 192 V. AEROSOL PRODUCTS 193 A.
NEBULIZERS 193 B. METERED-DOSE INHALERS (MDIS) 195 C. POWDER INHALERS
195 VI. TRANSDERMAL PATCHES 196 REVIEW QUESTIONS 197 BIBLIOGRAPHY 197
CHAPTER 18 PHARMACEUTICAL POLYMERS 199 LEARNING OBJECTIVES 199 I.
INTRODUCTION 199 II. DEFINITIONS AND ARCHITECTURES OF POLYMERS 199 HI.
POLYMER MOLECULAR WEIGHT AND WEIGHT DISTRIBUTION 204 IV. BIODEGRADABLITY
AND BIOCOMPATIBILITY 205 V. POLYMER SOLUBILITY 205 VI. BLOCK COPOLYMERS
206 VII. INTELLIGENT OR STIMULI-SENSITIVE POLYMERS 207 VIII.
WATER-SOLUBLE POLYMERS 208 IX. BIOADHESIVE/MUCOADHESIVE POLYMERS 209 XVI
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY REVIEW QUESTIONS 209
BIBLIOGRAPHY 210 CHAPTER 19 DRUG DELIVERY SYSTEMS 211 LEARNING
OBJECTIVES 211 I. INTRODUCTION 211 II. PRODRUGS 212 III. SOLUBLE
MACROMOLECULAR CARRIERS 213 IV. PARTICULATE CARRIER SYSTEMS 214 A.
LIPOSOMES 215 1. TYPES OF LIPOSOMES 215 2. FABRICATION OF LIPOSOMES 216
B. MICROPARTICLES AND NANOPARTICLES 218 1. FABRICATION OF
MICROPARTICULATES 219 C. NANOPARTICLES 223 V. ORAL DRUG DELIVERY 224 VI.
ALTERNATIVE ROUTES OF DELIVERY 225 A. BUCCAL AND SUBLINGUAL DRUG
DELIVERY 225 B. NASAL DRUG DELIVERY 226 C. PULMONARY DRUG DELIVERY 227
D. OCULAR DRUG DELIVERY 227 E. RECTAL DRUG DELIVERY 228 F. VAGINAL DRUG
DELIVERY 228 REVIEW QUESTIONS 229 BIBLIOGRAPHY 229 CHAPTER 20 PROTEIN-
AND PEPTIDE-BASED DOSAGE FORMS 231 LEARNING OBJECTIVES 231 I.
INTRODUCTION 231 II. STRUCTURE OF PEPTIDES AND PROTEINS 232 A. PRIMARY
STRUCTURE 234 B. SECONDARY STRUCTURE 235 C. TERTIARY STRUCTURE 235 D.
QUATERNARY STRUCTURES 235 III. HYDROPHOBICITY OF PEPTIDES AND PROTEINS
235 IV. SOLUBILITY OF PEPTIDES AND PROTEINS 236 V. INSTABILITY OF
PEPTIDES AND PROTEINS 237 A. PHYSICAL INSTABILITY 237 1. DENATURATION
237 2. AGGREGATION AND PRECIPITATION 238 3. SURFACE ADSORPTION 238 TABLE
OF CONTENTS XVII B. CHEMICAL INSTABILITY 238 1. HYDROLYSIS 239 2.
DEAMIDATION 239 3. OXIDATION 239 4. RACEMIZATION 240 5. DISULFIDE
EXCHANGE 240 VI. FORMULATION OF PROTEINS AND PEPTIDES 240 A. ADDITIVES
240 B. LYOPHILIZED PROTEINS 241 C. CHEMICAL MODIFICATION 242 D.
PEGYLATION 242 VII. ANTIBODY-BASED THERAPY AND DELIVERY 242 VIII.
ANTIGENICITY AND IMMUNOGENICITY 244 REVIEW QUESTIONS 244 BIBLIOGRAPHY
245 CHAPTER 21 BIOTECHNOLOGY-BASED DOSAGE FORMS 247 LEARNING OBJECTIVES
247 I. INTRODUCTION 247 II. GENES AND GENE EXPRESSION 247 III. GENE
SILENCING 248 IV. CLASSIFICATION OF GENE-SILENCING TECHNOLOGIES 249 A.
ANTISENSE OLIGONUCLEOTIDES 249 B. TRIPLEX-FORMING OLIGONUCLEOTIDES 250
C. PEPTIDE NUCLEIC ACIDS 250 D. ANTISENSE RNA 250 E. APTAMERS 250 F.
RIBOZYMES 251 G. RNA INTERFERENCE 251 V. GENE THERAPY 251 A. RETROVIRAL
VECTOR 252 1. MOLONEY MURINE LEUKEMIA VIRUSES 253 2. LENTIVIRUSES 253 B.
ADENOVIRAL VECTORS 254 C. ADENO-ASSOCIATED VIRUS VECTORS 254 D. HERPES
SIMPLEX VIRUS VECTORS 254 E. GENE EXPRESSION PLASMID 254 F. GENE
DELIVERY SYSTEMS 255 1. LIPID-BASED GENE DELIVERY 256 2. PEPTIDE-BASED
GENE DELIVERY 257 3. POLYMER-BASED GENE DELIVERY 258 REVIEW QUESTIONS
258 BIBLIOGRAPHY 259 XVIII PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY
CHAPTER 22 ANSWERS TO REVIEW QUESTIONS 261 CHAPTER 1: DRUG DEVELOPMENT
AND REGULATORY PROCESS 261 CHAPTER 2: PHARMACEUTICAL AND FORMULATION
CONSIDERATIONS 261 CHAPTER 3: BIOPHARMACEUTICAL AND PHYSIOLOGICAL
CONSIDERATIONS 266 CHAPTER 4: COMPLEXATION AND PROTEIN BINDING 267
CHAPTER 5: CHEMICAL KINETICS AND STABILITY 269 CHAPTER 6: INTERFACIAL
PHENOMENON 270 CHAPTER 7: RHEOLOGY 271 CHAPTER 8: DISPERSE SYSTEM BASICS
272 CHAPTER 9: SURFACTANTS AND MICELLES 275 CHAPTER 10: PHARMACEUTICAL
SUSPENSIONS 276 CHAPTER 11: PHARMACEUTICAL EMULSIONS 277 CHAPTER 12:
PHARMACEUTICAL SOLUTIONS 279 CHAPTER 13: TABLETS 279 CHAPTER 14:
CAPSULES 280 CHAPTER 15: INJECTABLE DOSAGE FORMS 280 CHAPTER 16:
SEMISOLID DOSAGE FORMS 281 CHAPTER 17: INSERTS, IMPLANTS, AND DEVICES
281 CHAPTER 18: PHARMACEUTICAL POLYMERS 281 CHAPTER 19: DRUG DELIVERY
SYSTEMS 282 CHAPTER 20: PROTEIN- AND PEPTIDE-BASED DOSAGE FORMS 283
CHAPTER 21: BIOTECHNOLOGY-BASED DOSAGE FORMS 283 INDEX 285
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| adam_txt |
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY RAM I. MAHATO CRC PRESS
TAYLOR & FRANCIS GROUP BOCA RATON LONDON NEWYORV CRC PRESS IS AN IMPRINT
OF THE TAYLOR & FRANCIS GROUP, AN INFORMA BUSINESS TABLE OF CONTENTS
LIST OF ILLUSTRATIONS XIX LIST OF TABLES XXIII FOREWORD XXV PREFACE
XXVII ACKNOWLEDGMENTS XXIX ABOUT THE AUTHOR XXXI CHAPTER 1 DRUG
DEVELOPMENT AND REGULATORY PROCESS 1 LEARNING OBJECTIVES 1 I.
INTRODUCTION 1 II. IDENTIFICATION OF NEW THERAPEUTIC MOLECULES 2 A.
EXTRACTION FROM PLANTS 2 B. ORGANIC SYNTHESIS 3 C. USE OF ANIMALS 4 D.
GENETIC ENGINEERING 4 E. GENE THERAPY 4 III. PRECLINICAL RESEARCH 4 IV.
FORMULATION DEVELOPMENT 5 V. REGULATORY ISSUES 5 A. INVESTIGATIONAL NEW
DRUG (IND) APPLICATION 5 B. CLINICAL TRIALS 6 1. PHASE I CLINICAL TRIALS
6 2. PHASE II CLINICAL TRIALS 6 3. PHASE III CLINICAL TRIALS 7 C. NEW
DRUG APPLICATION (NDA) 7 D. APPROVAL AND POSTMARKETING SURVEILLANCE 7 E.
ABBREVIATED NEW DRUG APPLICATION (ANDA) 8 F. ROLE OF FDA'S ADVISORY
COMMITTEES 8 REVIEW QUESTIONS 8 BIBLIOGRAPHY 9 CHAPTER 2 PHARMACEUTICAL
AND FORMULATION CONSIDERATIONS 11 LEARNING OBJECTIVES 11 I. INTRODUCTION
11 II. ADVANTAGES OF PHARMACEUTICAL DOSAGE FORMS 11 VIII PHARMACEUTICAL
DOSAGE FORMS AND DRUG DELIVERY III. INFLUENTIAL FACTORS IN DOSAGE FORM
DESIGN 12 A. MOLECULAR SIZE AND VOLUME 13 B. DRUG SOLUBILITY AND PH 14
C. LIPOPHILICITY AND PARTITION COEFFICIENT 16 D. POLYMORPHISM 17 E.
STABILITY 19 F. PKA/DISSOCIATION CONSTANTS 20 G. DEGREE OF LONIZATION
AND PH-PARTITION THEORY 24 1. LIMITATIONS OF PH-PARTITION THEORY 24
REVIEW QUESTIONS 25 BIBLIOGRAPHY 26 CHAPTER 3 BIOPHARMACEUTICAL AND
PHYSIOLOGICAL CONSIDERATIONS 29 LEARNING OBJECTIVES 29 I. INTRODUCTION
29 II. DRUG TRANSPORT ACROSS A POLYMERIC BARRIER 30 III. FICK'S LAWS OF
DIFFUSION 30 A. FICK'S FIRST LAW OF DIFFUSION 30 B. FICK'S SECOND LAW OF
DIFFUSION 32 1. STEADY-STATE CONDITIONS 32 2. LAG TIME 34 IV. PORE
DIFFUSION 34 V. MATRIX (MONOLITHIC)-TYPE NONDEGRADABLE DEVICE 35 VI.
BIOLOGICAL MEMBRANES AND DRUG ABSORPTION 36 A. PASSIVE TRANSPORT 37 1.
SIMPLE DIFFUSION 37 2. CARRIER-MEDIATED TRANSPORT 37 3. CHANNEL-MEDIATED
TRANSPORT 37 B. ACTIVE TRANSPORT 37 VII. FICK'S LAW OF DIFFUSION AND
DRUG ABSORPTION 38 VIII. DISSOLUTION RATE AND NOYES-WHITNEY EQUATION OF
DISSOLUTION 40 IX. FACTORS INFLUENCING DISSOLUTION RATE 41 A.
PHYSICOCHEMICAL PROPERTIES 41 B. THICKNESS OF DIFFUSION LAYER 42 C.
GASTROINTESTINAL FLUIDS 42 D. PARTICLE SIZE 42 E. CRYSTALLINITY 42 F.
POROSITY AND TORTUOSITY OF SOLID PARTICLES 43 G. TEMPERATURE 43 H.
SURFACTANTS 43 X. DRUG ABSORPTION AND BIOAVAILABILITY 43 REVIEW
QUESTIONS 43 BIBLIOGRAPHY 45 TABLE OF CONTENTS CHAPTER 4 COMPLEXATION
AND PROTEIN BINDING 47 LEARNING OBJECTIVES 47 I. INTRODUCTION 47 II.
TYPES OF COMPLEXATION 47 A. COORDINATION COMPLEXES 48 B. MOLECULAR
COMPLEXES 48 C. DRUG COMPLEXES 50 D. POLYMER COMPLEXES 50 E. INCLUSION
COMPLEXES 50 III. DRUG INTERACTION WITH PLASMA PROTEINS 52 IV. BINDING
EQUILIBRIA 52 A. PROTEIN BINDING 54 V. IMPACT OF PLASMA PROTEIN BINDING
ON DOSING REGIMENS 55 REVIEW QUESTIONS 56 BIBLIOGRAPHY 57 CHAPTER 5
CHEMICAL KINETICS AND STABILITY 59 LEARNING OBJECTIVES 59 I.
INTRODUCTION 59 II. RATES AND ORDER OF REACTION 59 A. ZERO-ORDER
REACTIONS 60 B. FIRST-ORDER REACTIONS 61 C. SECOND-ORDER KINETICS 63
III. FACTORS AFFECTING REACTION KINETICS 65 A. CATALYSIS 65 B. EFFECT OF
TEMPERATURE 65 C. EFFECT OF SOLVENT 67 D. EFFECT OF PH 67 E. PRESENCE OF
ADDITIVES 67 IV. PATHWAYS AND PREVENTION OF CHEMICAL DECOMPOSITION OF
DRUGS 68 A. HYDROLYSIS 68 1. CONTROL OF DRUG HYDROLYSIS 69 B. OXIDATION
70 1. CONTROL OF DRUG OXIDATION 72 C. PHOTOLYSIS 72 1. CONTROL OF
PHOTODEGRADATION OF DRUGS 72 REVIEW QUESTIONS 73 BIBLIOGRAPHY 73 CHAPTER
6 INTERFACIAL PHENOMENA 75 LEARNING OBJECTIVES 75 I- INTRODUCTION 75 X
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY II. LIQUID INTERFACES 75
A. SURFACE AND INTERFACIAL TENSIONS 75 B. SURFACE FREE ENERGY 76 III.
ADSORPTION AT SOLID-GAS INTERFACES 77 A. PHYSICAL ADSORPTION 77 B.
CHEMICAL ADSORPTION 78 C. ADSORPTION ISOTHERMS 78 1. FREUNDLICH
ADSORPTION ISOTHERM 78 2. LANGMUIR ADSORPTION ISOTHERM 79 3. BET
ADSORPTION ISOTHERM 80 4. TYPE OF ISOTHERMS 80 IV. ADSORPTION AT
SOLID-LIQUID INTERFACE 81 A. FACTORS AFFECTING ADSORPTION FROM SOLUTION
81 B. APPLICATION OF ADSORPTION 82 V. WETTABILITY AND WETTING AGENTS 83
A. WETTING AGENTS 83 VI. PROTEIN ADSORPTION 84 REVIEW QUESTIONS 84
BIBLIOGRAPHY 85 CHAPTER 7 RHEOLOGY 87 LEARNING OBJECTIVES 87 I.
INTRODUCTION 87 II. NEWTONIAN FLOW 87 A. TEMPERATURE DEPENDENCE AND
VISCOSITY OF LIQUIDS 88 III. NON-NEWTONIAN FLOW 88 A. PLASTIC FLOW 88 B.
PSEUDOPLASTIC FLOW 90 C. DILATANTFLOW 90 IV. THIXOTROPY 91 A. HYSTERESIS
LOOP 91 B. NEGATIVE THIXOTROPY 93 V. PHARMACEUTICAL APPLICATIONS OF
RHEOLOGY 93 REVIEW QUESTIONS 94 BIBLIOGRAPHY 94 CHAPTER 8 DISPERSE
SYSTEM BASICS 95 LEARNING OBJECTIVES 95 I. INTRODUCTION 95 II. TYPES OF
COLLOIDAL SYSTEMS 96 A. LYOPHILIC COLLOIDS 96 B. LYOPHOBIC COLLOIDS 96
C. ASSOCIATION COLLOIDS 97 TABLE OF CONTENTS XI III. KINETIC PROPERTIES
OF COLLOIDS 97 A. BROWNIAN MOVEMENT 97 1. DIFFUSION 96 2. SEDIMENTATION
96 IV. ELECTRICAL PROPERTIES 99 A. IONIZATION 99 B. ION ADSORPTION 100
C. ION DISSOLUTION 100 V. ELECTROSTATIC EFFECT 100 VI. ELECTRICAL DOUBLE
LAYER 100 A. NERST AND ZETA POTENTIALS 102 B. DLVO THEORY 102 C.
ELECTROPHORETIC PHENOMENA 102 VII. STABILITY OF COLLOIDS 103 A.
AGGREGATION 104 B. COAGULATION 104 C. FLOCCULATION 104 REVIEW QUESTIONS
104 BIBLIOGRAPHY 105 CHAPTER 9 SURFACTANTS AND MICELLES 107 LEARNING
OBJECTIVES 107 I. INTRODUCTION 107 II. SURFACTANTS 107 A. TYPES OF
SURFACTANTS 108 1. ANIONIC SURFACTANTS 108 2. CATIONIC SURFACTANTS 109
3. NONIONIC SURFACTANTS 109 4. AMPHOLYTIC SURFACTANTS 109 III. HLB
SYSTEMS 110 IV MICELLES 111 A. TYPES OF MICELLES 114 B. CMC AND MICELLAR
SIZE 114 V. MICELLAR SOLUBILIZATION 115 A. FACTORS AFFECTING
SOLUBILIZATION 115 1. NATURE OF SURFACTANTS 115 2. NATURE OF
SOLUBILIZATES 116 3. EFFECT OF TEMPERATURE 116 4. EFFECT OF PH 116 B.
PHARMACEUTICAL APPLICATIONS OF MICELLAR SOLUBILIZATION 116 C.
THERMODYNAMICS OF SOLUBILIZATION 117 VI. KRAFFT POINT 118 VII. CLOUD
POINT 119 XII PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY REVIEW
QUESTIONS 119 BIBLIOGRAPHY 120 CHAPTER 10 PHARMACEUTICAL SUSPENSIONS 123
LEARNING OBJECTIVES 123 I. INTRODUCTION 123 II. CLASSIFICATION OF
SUSPENSIONS 123 III. CHARACTERISTICS OF PHARMACEUTICAL SUSPENSIONS 124
IV. FORMULATION OF SUSPENSIONS 125 V. FLOCCULATION AND DEFLOCCULATION
126 A. PROPERTIES OF DEFLOCCULATED (DISPERSED) PARTICLES 129 B.
PROPERTIES OF FLOCCULATED PARTICLES 129 VI. SUSPENSION STABILITY 130 A.
ADHESION OF SUSPENSION PARTICLES TO CONTAINERS 130 B. SEDIMENTATION
PARAMETERS 130 C. SEDIMENTATION AND STOKE'S LAW 131 REVIEW QUESTIONS 132
BIBLIOGRAPHY 133 CHAPTER 11 PHARMACEUTICAL EMULSIONS 135 LEARNING
OBJECTIVES 135 I. INTRODUCTION 135 II. ADVANTAGES OF EMULSION DOSAGE
FORMS 135 III. TYPES OF EMULSIONS 135 A. OIL-IN-WATER EMULSIONS 136 B.
WATER-IN-OIL EMULSIONS 136 C. MULTIPLE EMULSIONS 137 D. MICROEMULSIONS
137 IV. ROLES OF INTERFACIAL FREE ENERGY ON EMULSIFICATION 137 V.
FORMULATIONS OF EMULSIONS 138 VI. EMULSIFYING AGENTS 138 A. SURFACTANTS
140 B. HYDROPHILIC COLLOIDS 140 C. FINELY DIVIDED SOLID PARTICLES 141
VII. TYPES OF INSTABILITY IN EMULSIONS 141 A. CREAMING AND SEDIMENTATION
141 B. BREAKING AND COALESCENCE 142 C. PHASE INVERSION 143 D. MICROBIAL
GROWTH 143 REVIEW QUESTIONS 143 BIBLIOGRAPHY 144 TABLE OF CONTENTS
CHAPTER 12 PHARMACEUTICAL SOLUTIONS 145 LEARNING OBJECTIVES 145 I.
INTRODUCTION 145 II. PH AND SOLUBILITY 146 III. BUFFER AND BUFFER
CAPACITY 146 IV. VEHICLES 148 V. TYPES OF SOLUTIONS 148 A. SYRUPS 148 B.
ELIXIRS 149 C. TINCTURES 149 D. MISCELLANEOUS SOLUTIONS 149 VI. DRY OR
LYOPHILIZED MIXTURES FOR SOLUTION 150 REVIEW QUESTIONS 150 BIBLIOGRAPHY
150 CHAPTER 13 TABLETS 153 LEARNING OBJECTIVES 153 I. INTRODUCTION 153
II. TYPES OF TABLETS 153 A. SWALLOWABLE TABLETS 153 B. EFFERVESCENT
TABLETS 154 C. CHEWABLE TABLETS 154 D. BUCCAL AND SUBLINGUAL TABLETS 154
E. LOZENGES 154 F. COATED TABLETS 154 G. CONTROLLED-RELEASE TABLETS 155
H. IMMEDIATE-RELEASE TABLETS 156 III. TABLET FORMULATION 156 A. DILUENTS
156 B. ADSORBENTS 157 C. MOISTENING AGENTS 157 D. BINDING AGENTS 157 E.
GLIDANTS 158 F. LUBRICANTS 158 G. DISINTEGRANTS 158 H. MISCELLANEOUS 159
IV POWDER FLOW AND COMPRESSIBILITY 159 V. MANUFACTURING OF TABLETS 159
VI. RELATIONSHIP AMONG DISINTEGRATION. DISSOLUTION, AND ABSORPTION 160
VII. EVALUATION OF TABLETS 161 REVIEW QUESTIONS 161 BIBLIOGRAPHY 163 XIV
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY CHAPTER 14 CAPSULES 165
LEARNING OBJECTIVES 165 I. INTRODUCTION 165 II. HARD GELATIN CAPSULES
166 A. ADVANTAGES AND DISADVANTAGES OF HARD GELATIN CAPSULES 166 B.
FORMULATION OF HARD GELATIN CAPSULES 167 III. SOFT GELATIN CAPSULES 168
A. FORMULATION OF SOFT GELATIN CAPSULES 169 IV. EVALUATION OF CAPSULES
170 REVIEW QUESTIONS 171 BIBLIOGRAPHY 171 CHAPTER 15 INJECTABLE DOSAGE
FORMS 173 LEARNING OBJECTIVES 173 I. INTRODUCTION 173 II. ISOTONICITY
174 III. PARENTERAL ROUTES OF ADMINISTRATION 174 A. INTRAVENOUS ROUTE
174 B. INTRAMUSCULAR ROUTE 175 C. SUBCUTANEOUS ROUTE 175 D. OTHER ROUTES
175 IV. FORMULATION OF PARENTERAL PRODUCTS 176 A. PHYSICOCHEMICAL
PROPERTIES OF THE DRUG 176 B. EXCIPIENTS IN PARENTERAL FORMULATIONS 176
C. VEHICLES 177 V. STERILIZATION OF PARENTERAL PRODUCTS 177 A.
FILTRATION 177 B. DRY HEAT STERILIZATION 178 C. STEAM STERILIZATION 178
D. RADIATION STERILIZATION 178 VI. TYPES OF PARENTERAL DOSAGE FORMS 178
A. SOLUTIONS 178 B. SUSPENSIONS 179 C. EMULSIONS 179 D. DRY POWDERS 179
VII. EVALUATION OF INJECTABLE PRODUCTS 179 A. STERILITY 180 B. PYROGENS
180 C. PANICULATE MATTERS 180 REVIEW QUESTIONS 181 BIBLIOGRAPHY 181
TABLE OF CONTENTS XV CHAPTER 16 SEMISOLID DOSAGE FORMS 183 LEARNING
OBJECTIVES 183 I. INTRODUCTION 183 II. OINTMENTS 183 A. TYPES OF
OINTMENT BASES 183 1. HYDROCARBON BASES 184 2. ABSORPTION BASES 184 3.
EMULSION BASES 184 4. WATER-SOLUBLE BASES 185 B. INCORPORATION OF DRUGS
INTO OINTMENT 185 III. CREAMS 185 IV GELS 186 V LOTIONS 187 VI. PASTES
187 REVIEW QUESTIONS 187 BIBLIOGRAPHY 188 CHAPTER 17 INSERTS, IMPLANTS,
AND DEVICES 189 LEARNING OBJECTIVES 189 I. INTRODUCTION 189 II. INSERTS
189 III. IMPLANTS 191 IV. SUPPOSITORIES 192 V. AEROSOL PRODUCTS 193 A.
NEBULIZERS 193 B. METERED-DOSE INHALERS (MDIS) 195 C. POWDER INHALERS
195 VI. TRANSDERMAL PATCHES 196 REVIEW QUESTIONS 197 BIBLIOGRAPHY 197
CHAPTER 18 PHARMACEUTICAL POLYMERS 199 LEARNING OBJECTIVES 199 I.
INTRODUCTION 199 II. DEFINITIONS AND ARCHITECTURES OF POLYMERS 199 HI.
POLYMER MOLECULAR WEIGHT AND WEIGHT DISTRIBUTION 204 IV. BIODEGRADABLITY
AND BIOCOMPATIBILITY 205 V. POLYMER SOLUBILITY 205 VI. BLOCK COPOLYMERS
206 VII. INTELLIGENT OR STIMULI-SENSITIVE POLYMERS 207 VIII.
WATER-SOLUBLE POLYMERS 208 IX. BIOADHESIVE/MUCOADHESIVE POLYMERS 209 XVI
PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY REVIEW QUESTIONS 209
BIBLIOGRAPHY 210 CHAPTER 19 DRUG DELIVERY SYSTEMS 211 LEARNING
OBJECTIVES 211 I. INTRODUCTION 211 II. PRODRUGS 212 III. SOLUBLE
MACROMOLECULAR CARRIERS 213 IV. PARTICULATE CARRIER SYSTEMS 214 A.
LIPOSOMES 215 1. TYPES OF LIPOSOMES 215 2. FABRICATION OF LIPOSOMES 216
B. MICROPARTICLES AND NANOPARTICLES 218 1. FABRICATION OF
MICROPARTICULATES 219 C. NANOPARTICLES 223 V. ORAL DRUG DELIVERY 224 VI.
ALTERNATIVE ROUTES OF DELIVERY 225 A. BUCCAL AND SUBLINGUAL DRUG
DELIVERY 225 B. NASAL DRUG DELIVERY 226 C. PULMONARY DRUG DELIVERY 227
D. OCULAR DRUG DELIVERY 227 E. RECTAL DRUG DELIVERY 228 F. VAGINAL DRUG
DELIVERY 228 REVIEW QUESTIONS 229 BIBLIOGRAPHY 229 CHAPTER 20 PROTEIN-
AND PEPTIDE-BASED DOSAGE FORMS 231 LEARNING OBJECTIVES 231 I.
INTRODUCTION 231 II. STRUCTURE OF PEPTIDES AND PROTEINS 232 A. PRIMARY
STRUCTURE 234 B. SECONDARY STRUCTURE 235 C. TERTIARY STRUCTURE 235 D.
QUATERNARY STRUCTURES 235 III. HYDROPHOBICITY OF PEPTIDES AND PROTEINS
235 IV. SOLUBILITY OF PEPTIDES AND PROTEINS 236 V. INSTABILITY OF
PEPTIDES AND PROTEINS 237 A. PHYSICAL INSTABILITY 237 1. DENATURATION
237 2. AGGREGATION AND PRECIPITATION 238 3. SURFACE ADSORPTION 238 TABLE
OF CONTENTS XVII B. CHEMICAL INSTABILITY 238 1. HYDROLYSIS 239 2.
DEAMIDATION 239 3. OXIDATION 239 4. RACEMIZATION 240 5. DISULFIDE
EXCHANGE 240 VI. FORMULATION OF PROTEINS AND PEPTIDES 240 A. ADDITIVES
240 B. LYOPHILIZED PROTEINS 241 C. CHEMICAL MODIFICATION 242 D.
PEGYLATION 242 VII. ANTIBODY-BASED THERAPY AND DELIVERY 242 VIII.
ANTIGENICITY AND IMMUNOGENICITY 244 REVIEW QUESTIONS 244 BIBLIOGRAPHY
245 CHAPTER 21 BIOTECHNOLOGY-BASED DOSAGE FORMS 247 LEARNING OBJECTIVES
247 I. INTRODUCTION 247 II. GENES AND GENE EXPRESSION 247 III. GENE
SILENCING 248 IV. CLASSIFICATION OF GENE-SILENCING TECHNOLOGIES 249 A.
ANTISENSE OLIGONUCLEOTIDES 249 B. TRIPLEX-FORMING OLIGONUCLEOTIDES 250
C. PEPTIDE NUCLEIC ACIDS 250 D. ANTISENSE RNA 250 E. APTAMERS 250 F.
RIBOZYMES 251 G. RNA INTERFERENCE 251 V. GENE THERAPY 251 A. RETROVIRAL
VECTOR 252 1. MOLONEY MURINE LEUKEMIA VIRUSES 253 2. LENTIVIRUSES 253 B.
ADENOVIRAL VECTORS 254 C. ADENO-ASSOCIATED VIRUS VECTORS 254 D. HERPES
SIMPLEX VIRUS VECTORS 254 E. GENE EXPRESSION PLASMID 254 F. GENE
DELIVERY SYSTEMS 255 1. LIPID-BASED GENE DELIVERY 256 2. PEPTIDE-BASED
GENE DELIVERY 257 3. POLYMER-BASED GENE DELIVERY 258 REVIEW QUESTIONS
258 BIBLIOGRAPHY 259 XVIII PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY
CHAPTER 22 ANSWERS TO REVIEW QUESTIONS 261 CHAPTER 1: DRUG DEVELOPMENT
AND REGULATORY PROCESS 261 CHAPTER 2: PHARMACEUTICAL AND FORMULATION
CONSIDERATIONS 261 CHAPTER 3: BIOPHARMACEUTICAL AND PHYSIOLOGICAL
CONSIDERATIONS 266 CHAPTER 4: COMPLEXATION AND PROTEIN BINDING 267
CHAPTER 5: CHEMICAL KINETICS AND STABILITY 269 CHAPTER 6: INTERFACIAL
PHENOMENON 270 CHAPTER 7: RHEOLOGY 271 CHAPTER 8: DISPERSE SYSTEM BASICS
272 CHAPTER 9: SURFACTANTS AND MICELLES 275 CHAPTER 10: PHARMACEUTICAL
SUSPENSIONS 276 CHAPTER 11: PHARMACEUTICAL EMULSIONS 277 CHAPTER 12:
PHARMACEUTICAL SOLUTIONS 279 CHAPTER 13: TABLETS 279 CHAPTER 14:
CAPSULES 280 CHAPTER 15: INJECTABLE DOSAGE FORMS 280 CHAPTER 16:
SEMISOLID DOSAGE FORMS 281 CHAPTER 17: INSERTS, IMPLANTS, AND DEVICES
281 CHAPTER 18: PHARMACEUTICAL POLYMERS 281 CHAPTER 19: DRUG DELIVERY
SYSTEMS 282 CHAPTER 20: PROTEIN- AND PEPTIDE-BASED DOSAGE FORMS 283
CHAPTER 21: BIOTECHNOLOGY-BASED DOSAGE FORMS 283 INDEX 285 |
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| discipline | Chemie / Pharmazie Medizin |
| discipline_str_mv | Chemie / Pharmazie Medizin |
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| id | DE-604.BV022501098 |
| illustrated | Illustrated |
| index_date | 2024-07-02T17:55:31Z |
| indexdate | 2024-07-09T20:58:58Z |
| institution | BVB |
| isbn | 9780849392856 0849392853 |
| language | English |
| lccn | 2007061452 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-015708152 |
| oclc_num | 78072834 |
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| owner | DE-29T DE-19 DE-BY-UBM |
| owner_facet | DE-29T DE-19 DE-BY-UBM |
| physical | XXXI, 300 S. graph. Darst. |
| publishDate | 2007 |
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| publisher | CRC Press |
| record_format | marc |
| series2 | CRC Press pharmacy education series |
| spelling | Mahato, Ram I. Verfasser aut Pharmaceutical dosage forms and drug delivery Ram I. Mahato Boca Raton, FL CRC Press 2007 XXXI, 300 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier CRC Press pharmacy education series Includes bibliographical references and index Médicaments - Administration - Dispositifs Médicaments - Formes pharmaceutiques Drugs Dosage forms Drug delivery systems Therapeutisches System (DE-588)4267580-7 gnd rswk-swf Therapeutisches System (DE-588)4267580-7 s DE-604 GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015708152&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Mahato, Ram I. Pharmaceutical dosage forms and drug delivery Médicaments - Administration - Dispositifs Médicaments - Formes pharmaceutiques Drugs Dosage forms Drug delivery systems Therapeutisches System (DE-588)4267580-7 gnd |
| subject_GND | (DE-588)4267580-7 |
| title | Pharmaceutical dosage forms and drug delivery |
| title_auth | Pharmaceutical dosage forms and drug delivery |
| title_exact_search | Pharmaceutical dosage forms and drug delivery |
| title_exact_search_txtP | Pharmaceutical dosage forms and drug delivery |
| title_full | Pharmaceutical dosage forms and drug delivery Ram I. Mahato |
| title_fullStr | Pharmaceutical dosage forms and drug delivery Ram I. Mahato |
| title_full_unstemmed | Pharmaceutical dosage forms and drug delivery Ram I. Mahato |
| title_short | Pharmaceutical dosage forms and drug delivery |
| title_sort | pharmaceutical dosage forms and drug delivery |
| topic | Médicaments - Administration - Dispositifs Médicaments - Formes pharmaceutiques Drugs Dosage forms Drug delivery systems Therapeutisches System (DE-588)4267580-7 gnd |
| topic_facet | Médicaments - Administration - Dispositifs Médicaments - Formes pharmaceutiques Drugs Dosage forms Drug delivery systems Therapeutisches System |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015708152&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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