New formulation for drug controlled release

Author: Jia Weigao, Wenyuan
Publisher:
Publishing Time: 2005-04-01
Features: This book is based on the principles of being novel, practical, in-depth, and systematic, introducing new drug delivery systems for controlled release from three aspects: the speed, location, and time of drug release. The book consists of 13 chapters in the first part, including oral rapid-release preparations that accelerate drug release speed, such as oral disintegrating tablets, dispersible tablets, drospills, and self-emulsifying drug delivery systems, as well as sustained-release and controlled-release preparations that delay or control drug release speed, such as transdermal controlled-release preparations, injectable sustained-release and controlled-release preparations for peptides and protein drugs, etc. There are also control release preparations such as oral control release systems, non-gastrointestinal mucosal controlled-release preparations, implantable controlled-release preparations, and targeted preparations, as well as timed control release preparations such as pulsed-release drug delivery systems and self-regulating controlled-release drug delivery systems. Each dosage form is comprehensively introduced, including its historical evolution, meaning, characteristics, classification, applicable drugs, new excipients, new processes, release mechanism, and examples. The appendix lists guidelines for oral disintegrating tablets, sustained-release and controlled-release preparations, microcapsules, microspheres, and liposomes, as well as new drug classification and application material requirements. This book has certain reference value for improving the research and production level of drug formulations and dosage forms, developing new formulations, improving clinical medication levels, and understanding the forefront and prospects of pharmaceutical technology. It can be read by teachers and students of relevant majors in various universities and can also be used as a reference for scientific and technological personnel and professionals in pharmaceutical research, development, and production.
Table of Contents
Part I Oral Rapid-Release Preparations
Chapter 1 Historical Evolution 3
Chapter 2 Meaning and Characteristics 4
Chapter 3 Oral Disintegrating Tablets 5
Section 1 Overview 5
Subsection 1 Introduction 5
Subsection 2 Characteristics 8
Subsection 3 Applicable Drugs 9
Subsection 4 Oral Mucosal Drug Delivery Pathway 9
Section 2 Oral Rapid-Disintegrating Tablets 10
Subsection 1 Overview 10
Subsection 2 Common Excipients for Oral Rapid-Disintegrating Tablets 11
Subsection 3 Preparation Process 14
Subsection 4 Research on Ginkgo Biloba Oral Disintegrating Tablets 15
Section 3 Oral Rapid-Dissolving Tablets 16
Subsection 1 Overview 16
Subsection 2 Composition 17
Subsection 3 Preparation Process 18
Subsection 4 Discussion on Preparation Process 22
Subsection 5 Research on Tanshinone Oral Rapid-Dissolving Tablets 23
Section 4 Quality Control 25
Section 5 Problems and Solutions 26
Subsection 1 Drug Loading Problem 26
Subsection 2 Drug Hardness Problem 26
Subsection 3 Drug Taste Problem 27
Subsection 4 Preparation Process Problem 27
Subsection 5 Fragility Problem 27
References 28
Chapter 2 Dispersible Tablets 30
Section 1 Overview 30
Subsection 1 Definition 30
Subsection 2 Development 30
Subsection 3 Varieties 30
Subsection 4 Characteristics 32
Subsection 5 Mechanism of Dispersible Tablet Rapid Disintegration 33
Section 2 Formulation Design 34
Subsection 1 Drug Selection 34
Subsection 2 Common Excipients 34
Subsection 3 Formulation Optimization 37
Section 3 Preparation Process 38
Subsection 1 Preparation Methods 38
Subsection 2 Key Technologies in Preparation Process 39
Subsection 3 Application of New Excipients and Technologies in Dispersible Tablets 42
Section 4 Quality Control 43
Subsection 1 Disintegration Time 43
Subsection 2 Dispersion Uniformity 43
Subsection 3 Weight Variation 43
Subsection 4 Dissolution Test 43
Subsection 5 Hardness and Friability 43
Subsection 6 Bioavailability and Equivalence Evaluation 44
Section 5 Examples 45
References 46
Chapter 3 Drospills 49
Section 1 Overview 49
Subsection 1 Definition and Classification 49
Subsection 2 Development 50
Subsection 3 Varieties 51
Subsection 4 Characteristics 52
Subsection 5 Drug Release Mechanism 53
Section 2 Formulation Design 53
Subsection 1 Drug Selection 53
Subsection 2 Matrix and Cold Condensing Agent 54
Section 3 Preparation Process 56
Subsection 1 Preparation Principle 56
Subsection 2 Preparation Technology 57
Subsection 3 Preparation Process 57
Subsection 4 Development of Drospill Production Equipment 62
Section 4 Factors Affecting Drospill Preparation 62
Subsection 1 Factors Affecting Pellet Weight 62
Subsection 2 Factors Affecting Roundness 62
Subsection 3 Factors Affecting Dissolution Time or Dissolution 63
Subsection 4 Other Factors 63
Section 5 Quality Control of Drospills 63
Subsection 1 Characteristics 63
Subsection 2 Identification 64
Subsection 3 Tests 64
Subsection 4 Content Determination 64
Subsection 5 Dissolution Test 64
Section 6 Examples 66
References 69
Chapter 4 Self-Emulsifying Drug Delivery Systems 71
Section 1 Overview 71
Subsection 1 Definition 71
Subsection 2 Characteristics 71
Subsection 3 Development 72
Subsection 4 Mechanism of Self-Emulsification and Self-Microemulsification 72
Subsection 5 Physicochemical Properties 74
Subsection 6 Mechanism of Rapid Release 74
Subsection 7 Major Factors Affecting Oral Absorption of Drugs in SEDDS 75
Section 2 Formulation Composition 76
Subsection 1 Formulation Design Principles 76
Subsection 2 Applicable Drugs 78
Subsection 3 Oil Phase 78
Subsection 4 Surfactants 79
Subsection 5 Co-emulsifiers 79
Section 3 Quality Evaluation 80
Subsection 1 Self-Emulsification Rate 80
Subsection 2 Pseudo-Ternary Phase Diagram 81
Subsection 3 Drug Release Rate 81
Subsection 4 Particle Size 82
Subsection 5 Polarity of Emulsions Obtained After Self-Emulsification 82
References 82
Part II Sustained-Release and Controlled-Release Preparations
Chapter 5 Oral Sustained-Release and Controlled-Release Preparations 87
Section 1 Overview 87
Subsection 1 Definition 87
Subsection 2 Characteristics 87
Subsection 3 Types 88
Subsection 4 Basic Composition of Controlled-Release Preparations 90
Subsection 5 Differences 90
Subsection 6 Current Status 91
Section 2 Mechanism and Methods of Drug Release in Sustained-Release and Controlled-Release Preparations 94
Subsection 1 Classification According to System Structure and Polymer Properties 94
Subsection 2 Classification Based on Different Principles 102
Section 3 Common Sustained-Release and Controlled-Release Materials 109
Section 4 Applicable Drugs and Clinical Applications 110
Subsection 1 Applicable Drugs 110
Subsection 2 Clinical Applications 112
Section 5 Sustained-Release Preparations 113
Subsection 1 Characteristics 113
Subsection 2 Types 115
Subsection 3 Design 115
Subsection 4 Preparation Process Research 117
Section 6 Controlled-Release Preparations 127
Subsection 1 Characteristics 127
Subsection 2 Types 127
Subsection 3 Design and Composition 127
Subsection 4 Preparation Process Research 129
Section 7 In Vitro and In Vivo Evaluation Methods 135
Subsection 1 In Vitro Evaluation 135
Subsection 2 In Vivo Evaluation 139
Subsection 3 In Vitro-In Vivo Correlation Evaluation 142
Subsection 4 Safety Testing of Sustained-Release Preparations 143
References 143
Chapter 6 Transdermal Controlled-Release Preparations 145
Section 1 Overview 145
Subsection 1 Definition 145
Subsection 2 Development and Characteristics of Transdermal Drug Delivery Systems 145
Subsection 3 Types of Transdermal Drug Delivery Systems 146
Section 2 Factors Affecting Transdermal Absorption 147
Section 3 Methods to Promote Drug Transdermal Absorption 148
Subsection 1 Transdermal Absorption Promoters and Transdermal Absorption 148
Subsection 2 Iontophoresis and Transdermal Absorption 149
Subsection 3 Ultrasound and Transdermal Absorption 150
Subsection 4 Electroporation and Transdermal Absorption 151
Subsection 5 Other Technologies and Transdermal Absorption 152
Section 4 Research Methods for Transdermal Drug Diffusion 153
Subsection 1 In Vitro Transdermal Diffusion Research 153
Subsection 2 In Vivo Transdermal Absorption Research 157
Section 5 Transdermal Patches 158
Subsection 1 Overview 158
Subsection 2 Basic Types and Composition of Patches 159
Subsection 3 Design Characteristics of Transdermal Drug Delivery Systems 160
Subsection 4 Preparation Process Characteristics of Transdermal Drug Delivery Systems 162
Subsection 5 Quality Control of Patches 162
Subsection 6 Application Examples 163
Section 6 Patches 167
Subsection 1 Overview 167
Subsection 2 Classification of Patches 168
Subsection 3 Basic Structure of Patches 168
Subsection 4 Matrix of Patches 169
Subsection 5 Transdermal Absorption Promoters of Patches 170
Subsection 6 Preparation Process of Patches 171
Subsection 7 Quality Evaluation of Patches 171
Subsection 8 Research Progress of Patches 172
Subsection 9 Examples 172
Section 7 Acupoint Patches 175
Subsection 1 Overview 175
Subsection 2 Characteristics of Acupoint Drug Application 176
Subsection 3 Principles and Common Acupoints for Acupoint Patch Application 176
Subsection 4 Dosage Forms of Acupoint Patches 176
Subsection 7 Examples 177
References 179
Chapter 7 Injectable Sustained-Release and Controlled-Release Preparations for Peptide and Protein Drugs 181
Section 1 Overview 181
Subsection 1 Current Status 181
Subsection 2 Characteristics 181
Subsection 3 Stability 181
Subsection 4 Dosage Forms 182
Section 2 Injectable Sustained-Release Microspheres 182
Subsection 1 Overview 182
Subsection 2 Preparation Materials and Methods 185
Subsection 3 Peptide Microsphere Injectable Preparations 188
Subsection 4 Special Case of Protein Drug Microsphere Injectable Preparations—Vaccine Microsphere Injectable Preparations 192
Subsection 5 Problems in Research on Injectable Sustained-Release Microspheres 193
Section 3 Injectable Liposomal Preparations for Peptide and Enzyme Drugs 194
Subsection 1 Overview 194
Subsection 2 Preparation Materials and Methods of Liposomes 196
Subsection 3 Peptide and Enzyme Liposomes 197
Subsection 4 Immunoadjuvants 197
Section 4 Injectable Nanoparticle Preparations for Peptide and Protein Drugs 198
Subsection 1 Overview 198
Subsection 2 Preparation Materials and Methods of Nanoparticles 199
References 201
Part III Targeted Controlled-Release Preparations
Chapter 8 Oral Targeted Controlled-Release Systems 205
Section 1 Oral Gastric Targeted Controlled-Release Systems 205
Subsection 1 Mechanism of Gastric Retention Preparations 206
Subsection 2 Major Factors Affecting Buoyancy Performance of Gastric Buoyant Preparations 209
Subsection 3 Two Technologies Based on Buoyancy Mechanism 210
Subsection 4 Formulation Design 213
Subsection 5 Preparation Process 215
Subsection 6 Quality Evaluation 216
Section 2 Oral Colon Drug Delivery Controlled-Release Systems 218
Subsection 1 Overview 218
Subsection 2 Anatomy and Physiological Characteristics of Colon and Factors Affecting Drug Absorption in Colon 219
Subsection 3 Design Principles of Oral Colon Drug Delivery Systems 220
Subsection 4 Formulation Techniques for Colon Targeted Release 221
Subsection 5 Quality Evaluation 223
Section 3 Oral Small Intestinal Drug Delivery Controlled-Release Systems 226
Subsection 1 Overview 226
Subsection 2 Anatomy and Physiological Characteristics of Small Intestine 227
Subsection 3 Principles of Oral Small Intestinal Targeted Drug Delivery (pH-Sensitive Type) 227
Subsection 4 Preparation Process and Examples 228
Subsection 5 Quality Evaluation 232
References 233
Chapter 9 Non-Gastrointestinal Mucosal Controlled-Release Preparations 237
Section 1 Mucosal Absorption Animal Models 237
Subsection 1 In Vivo Absorption Animal Models 237
Subsection 2 In Situ Perfusion Animal Models 238
Subsection 3 Isolated Absorption Animal Models 239
Section 2 Oral Controlled-Release Preparations 240
Subsection 1 Physiological Characteristics of Oral Mucosa and Drug Absorption Process 240
Subsection 2 Bioadhesive Preparations 242
Subsection 3 Examples of Oral Controlled-Release Preparations 246
Section 3 Nasal Controlled-Release Preparations 249
Subsection 1 Overview 249
Subsection 2 Nasal Mucosal Absorption Promoters 252
Subsection 3 Nasal Drug Delivery Dosage Forms 252
Subsection 4 Research Models for Nasal Drug Delivery 253
Section 4 Ophthalmic Controlled-Release Preparations 254
Subsection 1 Ocular Tissue Structure and Drug Absorption Characteristics 255
Subsection 2 Ophthalmic Controlled-Release Preparations 258
Subsection 3 Quality Evaluation 260
Section 5 Uterine and Vaginal Mucosal Drug Delivery Systems 262
Subsection 1 Uterine Mucosal Drug Delivery System 263
Subsection 2 Vaginal Mucosal Drug Delivery 268
Section 6 Rectal Controlled-Release Drug Delivery System 274
Subsection 1 Physiology and Substance Absorption Characteristics of Rectal Mucosa 275
Subsection 2 Factors Affecting Rectal Absorption 275
Subsection 3 Research Progress of Rectal Controlled-Release Preparations 277
Subsection 4 Drugs for Rectal Drug Delivery 279
References 280
Chapter 10 Implantable Controlled-Release Preparations 284
Section 1 Overview 284
Subsection 1 Historical Evolution 284
Subsection 2 Applicable Drugs and Characteristics of Dosage Forms 285
Subsection 3 Carrier Materials 285
Subsection 4 Biocompatibility of Carrier Materials 286
Section 2 Types of Implants 287
Subsection 1 Solid Drug-Loaded Implants 287
Subsection 2 Implant Pump Preparations 289
Subsection 3 Injectable Implants 291
Section 3 Drug Release Mechanism in Implants 292
Subsection 1 Passive Diffusion Controlled-Release 293
Subsection 2 Erosion Degradation Mechanism 294
Subsection 3 Pulsed and Magnetic Controlled-Release Systems 294
Section 4 Preparation Process of Implants 294
Subsection 1 Direct Filling Method 294
Subsection 2 Press Mold Forming 295
Subsection 3 Melting Forming 295
Section 5 Application of Implants 296
Subsection 1 Hormone Drug Delivery 296
Subsection 2 Treatment of Tumors 296
Subsection 3 Ocular Implants 297
Subsection 4 Insulin Drug Delivery 298
Subsection 5 Psychotropic Drugs 298
References 298
Chapter 11 Targeted Preparations 300
Section 1 Overview 300
Subsection 1 Targeted Drug Transport Systems 301
Subsection 2 Classification of Targeted Preparations 303
Subsection 3 Biological Factors Related to Targeted Preparations 304
Subsection 4 Pharmacokinetic and Pharmacodynamic Evaluation of Targeted Preparations 306
Subsection 5 Quality Evaluation of Targeted Preparations 306
Section 2 Liposomes 307
Subsection 1 Composition and Properties of Liposomes 308
Subsection 2 In Vivo Distribution and Targeting of Liposomes 311
Subsection 3 Preparation and Evaluation of Liposomes 313
Subsection 4 Modification Research of Liposomes 316
Subsection 5 Vesicles 322
Section 3 Microspheres and Microcapsules 322
Subsection 1 In Vivo Distribution of Microspheres and Microcapsules 323
Subsection 2 Composition of Microspheres and Microcapsules 323
Subsection 3 Drug Release Patterns and Influencing Factors 324
Subsection 4 Preparation and Quality Evaluation of Microspheres and Microcapsules 325
Subsection 5 Preparation Examples 332
Section 4 Nanoparticles 337
Subsection 1 Targeting Mechanism of Nanoparticles 337
Subsection 2 Preparation of Nanoparticles 338
Subsection 3 Nanoparticle Formulation Process 340
Subsection 4 Modification of Nanoparticles 341
Subsection 5 Solid Lipid Nanoparticles 342
Section 5 Emulsions 343
Subsection 1 Emulsion Types 343
Subsection 2 Drug Release Mechanism of Emulsions 344
Subsection 3 Factors Affecting Emulsion Release Characteristics and Targeting 344
Subsection 4 Microemulsions 346
Subsection 5 Self-Emulsifying Drug Delivery Systems 348
Section 6 Active Targeted Preparations 349
Subsection 1 Modification of Drug Carriers 349
Subsection 2 Monoclonal Antibody Preparations 349
Subsection 3 Prodrugs 350
Section 7 Organ Targeted Preparations 350
Subsection 1 Liver Targeted Preparations 350
Subsection 2 Brain Targeted Preparations 352
Subsection 3 Bone Targeted Preparations 355
Subsection 4 Lung Targeted Preparations 357
Subsection 5 Renal Targeted Preparations 358
Subsection 6 Others 359
References 359
Part IV Timed Controlled-Release Preparations
Chapter 12 Pulsed-Release Controlled-Release Drug Preparations 365
Section 1 Overview 365
Subsection 1 Disease Time Rhythm 365
Subsection 2 Pulsed-Release Drug Delivery Systems 365
Section 2 Magnetic Controlled Pulsed-Release Drug Delivery 366
Subsection 1 Magnetic Preparations 366
Subsection 2 Magnetic Controlled Pulsed-Release Drug Delivery Systems 366
Section 3 Ultrasound Controlled Pulsed-Release Drug Delivery 369
Subsection 1 Scaffolding Preparation 369
Subsection 2 In Vitro and In Vivo Research 369
Subsection 3 Mechanism 372
Subsection 4 Prospects for Ultrasound-Triggered Pulsed Release 372
Section 4 Temperature Controlled Pulsed-Release Drug Delivery 372
Subsection 1 Utilizing Temperature-Sensitive Liposomes to Control Pulsed Release Technology 372
Subsection 2 Utilizing Temperature-Sensitive Hydrogels to Control Pulsed Release Technology 373
Section 5 Electrochemical Controlled Pulsed-Release Drug Delivery 374
Subsection 1 Electric Field Controlled Hyaluronic Acid Pulsed Drug Delivery Systems 374
Subsection 2 Electric Pulsed-Release Drug Delivery 376
Section 6 Light Controlled Pulsed-Release Drug Delivery 378
Section 7 Solubility Controlled Pulsed-Release Drug Delivery 379
Subsection 1 Utilizing Coating Layer to Control Pulsed Release Technology 380
Subsection 2 Utilizing Osmostic Pump Mechanism to Control Pulsed Release Technology 382
Subsection 3 Utilizing Hydrophilic Gel Swelling Mechanism to Control Pulsed Release Technology 383
Section 8 Microwave Controlled Pulsed-Release Drug Delivery 384
References 384
Chapter 13 Self-Regulating Controlled-Release Drug Preparations 387
Section 1 Overview 387
Subsection 1 Definition of Self-Regulating Controlled-Release Drug Preparations 387
Subsection 2 Drug Release Mechanism and Characteristics of Self-Regulating Controlled-Release Drug Preparations 387
Subsection 3 Materials of Self-Regulating Controlled-Release Preparations 388
Subsection 4 Application of Self-Regulating Controlled-Release Preparations 389
Subsection 5 Research Status and Prospects of Self-Regulating Controlled-Release Drug Preparations 389
Section 2 Self-Regulating Drug Controlled Release Systems 390
Subsection 1 pH-Sensitive Drug Release Systems 390
Subsection 2 Self-Regulating Drug Release Systems Based on Enzyme and Substrate Reaction 399
Subsection 3 Competitive Binding Type Insulin Controlled-Release System 407
Subsection 4 Triggered Drug Release Systems Controlled by Antibody and Antigen 410
Subsection 5 Glucose-Sensitive Systems Containing Boronic Acid Groups 415
Subsection 6 Chelating Agent Self-Regulating Release Systems 417
References 418
Appendix 423
Appendix 1 Minutes of Oral Disintegrating Tablet Dosage Form Characteristics and Quality Control Conference 425
Appendix 2 Guiding Principles for Sustained-Release and Controlled-Release Preparations 428
Appendix 3 Guiding Principles for Microcapsules, Microspheres, and Liposomes 432
Appendix 4 Supplementary Provisions of the "Measures for Drug Registration" (Trial) Appendix I: Classification and Application Material Requirements for Traditional Chinese Medicine and Natural Medicines 435
Appendix 5 Supplementary Provisions of the "Measures for Drug Registration" (Trial) Appendix II: Classification and Application Material Requirements for Chemical Drugs 443
Appendix 6 Supplementary Provisions of the "Measures for Drug Registration" (Trial) Appendix III: Requirements for Registration Classification and Application Material Items for Biologic Products 454