PHARMACEUTICAL PRODUCT DEVELOPMENT
CONTENTS CHAPTER INTRODUCTION AND OVERVIEW PHARMACEUTICAL PRODUCTS INFLUENCE OF PARTICLE PROPERTIES ON PHARMACEUTICAL QUALITY POWERFUL METHODS COMPLEMENTARY TO PARTICLE SIZING INTEGRATION OF PARTICLE SIZING METHODS WITH THEIR IN-USE SITUATION ADJACENCIES AND INTERACTIONS BETWEEN PARTICLES PARTICLE CHARACTERIZATION AND ITS IMPACT ON REGULATORY SUBMISSIONS FROM FORMULATION THROUGH TOXICOLOGY AND EFFICACY CONCLUSION CHAPTER STATES OF MATTER CRYSTALLINE SOLIDS CRYSTAL SYMMETRY EULER’S RELATIONSHIP CRYSTAL SYSTEMS MILLER INDICES SPACE LATTICES SOLID STATE BONDING ISOMORPHS AND POLYMORPHS ENANTIOMORPHS AND RACEMATES CRYSTAL HABIT CRYSTAL IMPERFECTIONS AMORPHOUS MATERIALS PARTICULATE SYSTEMS REFERENCES PRIMARY PARTICLE MANUFACTURING PARTICLE PRODUCTION METHODS—CONSTRUCTIVE METHODS—DESTRUCTIVE COMPLEX MANUFACTURING PROCESSES ? CHAPTER SAMPLING TECHNIQUES, ERRORS, AND MEASUREMENT BIAS INTRODUCTION SAMPLING FROM STATIONARY HEAPS SAMPLING FROM A FLOWING STREAM (PROCESS SAMPLING) SAMPLE SPLITTING SAMPLING OF PHARMACEUTICAL PARTICULATE SYSTEMS SAMPLING, PREPARATION, AND MEASUREMENT ERRORS PREPARATION AND MEASUREMENT ERRORS IN PARTICLE SIZE MEASUREMENTS MICROSCOPY SIEVING SEDIMENTATION LASER DIFFRACTION PARTICLE CHARACTERIZATION AND DATA EXPRESSION PARTICLE SIZE DIRECT IMAGING OPTICAL MICROSCOPY POLARIZED OPTICAL MICROSCOPY DARK-FIELD MICROSCOPY FLUORESCENCE MICROSCOPY TRANSMISSION ELECTRON MICROSCOPY SCANNING ELECTRON MICROSCOPY ENVIRONMENTAL SCANNING ELECTRON MICROSCOPY SCANNING TUNNELING MICROSCOPY AND ATOMIC FORCE MICROSCOPY INDIRECT IMAGING SINGLE PARTICLES POPULATIONS OF PARTICLES INERTIAL IMPACTION FILTRATION ANDREASEN PIPETTE VIRTUAL IMPINGER CENTRIFUGATION APPROACHES TO CALIBRATION VIBRATING ORIFICE MONODISPERSE AEROSOL GENERATOR SPINNING DISK GENERATORS CHARGE NEUTRALIZATION PARTICLE SIZE DIMENSIONS AND STATISTICS PARTICLE SIZE DESCRIPTORS PARTICLE SHAPE POWDER MIXING PARTICLE SIZE STATISTICS PRINCIPLES OF STATISTICAL INFERENCE MATHEMATICAL DISTRIBUTIONS MULTIMODAL DISTRIBUTIONS APPLICATIONS MEASURES OF DIAMETERS PARTICLE SURFACES—SPATIAL AND CHEMICAL DETECTION AUGER ELECTRON SPECTROSCOPY X-RAY PHOTOELECTRON SPECTROSCOPY SECONDARY ION MASS SPECTROSCOPY GAS ADSORPTION PARTICLE BULK—CHEMICAL PROPERTIES FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR) RAMAN SPECTROSCOPY THERMAL ANALYSES PARTICLE AND POWDER BEHAVIOR PHYSICAL PROPERTIES SIZE SHAPE SURFACE ROUGHNESS SURFACE AREA DENSITY PARTICLE ADHESION ELECTRICAL FORCES NONELECTRICAL FORCES ADHESION FORCE MEASUREMENTS FACTORS AFFECTING PARTICLE ADHESION PARTICLE MOTION IN BULK POWDERS POWDER FLOW FLUIDIZATION MIXING PARTICLE MOTION IN GASEOUS DISPERSIONS FREE MOLECULE REGIME CONTINUUM (STOKES’) REGIME SLIP FLOW REGIME CENTRIFUGAL SETTLING ACCELERATION, DECELERATION, AND CURVILINEAR MOTION PARTICLE MOTION IN LIQUID MEDIA DIFFUSION GRAVITATIONAL SEDIMENTATION FIELD-FLOW FRACTIONATION FLOW OF LIQUID DISPERSIONS BULK PARTICLE BEHAVIOR SELECTION OF THE APPROPRIATE PARTICLE SIZE EXPRESSION POWDER FLOW AND MIXING VIBRATION AND POWDER TRANSFER MIXING AND MILLING DISPERSION GRANULATION AND COMPRESSION PARTICULATE PHARMACEUTICAL PROCESSES AND PRODUCTS MANUFACTURING PROCESSES AFFECTED BY PARTICLE COMPOSITION AND BEHAVIOR PARTICLE COMPONENTS OF DOSAGE FORM PROCESSING STEPS IN FORMULATION AND DOSAGE FORM MANUFACTURE BLENDING GRANULATION FILLING BATCH AND CONTINUOUS PROCESSING PRODUCT AND INTERMEDIATE CHARACTERIZATION FINAL DOSAGE FORM PROPERTIES AFFECTING DOSAGE FORM PERFORMANCE MOISTURE ELECTROSTATIC CHARGE AERODYNAMIC BEHAVIOR STABILITY DRUG RELEASE DISINTEGRATION AND DEAGGREGATION DISSOLUTION SUMMARY REGULATORY CONSIDERATIONS FOR PHARMACEUTICAL DEVELOPMENT PRODUCT DEVELOPMENT REGULATORY SUBMISSIONS COMMERCIAL PRODUCTION CLINICAL APPLICATIONS OF PHARMACEUTICAL PARTICULATE SYSTEMS GENERAL BIOPHARMACEUTICS AND PHARMACOKINETICS ORAL DELIVERY BIOLOGY BIOPHARMACEUTICS PREPARATIONS PARENTERAL DELIVERY RESPIRATORY AND NASAL DELIVERY TRANSDERMAL AND TOPICAL DELIVERY BUCCAL AND SUBLINGUAL DELIVERY RECTAL DELIVERY VAGINAL DELIVERY CHAPTER 10 GENERAL CONCLUSIONS