MICROAEROSOLS: PHYSIOLOGY, PHARMACOLOGY, THERAPEUTICS
CONTENTS PART I: AERODYNAMIC BEHAVIOR 1 DEPOSITION MECHANICS OF PHARMACEUTICAL PARTICLES IN HUMAN AIRWAYS I INTRODUCTION II DEPOSITION MODEL FOR AEROSOLIZED DRUGS III RESULTS AND DISCUSSION REFERENCES 2 THERMODYNAMICS OF INHALED HYGROSCOPIC DRUGS II METHODS TO STUDY AEROSOL THERMODYNAMICS III DISCUSSION OF AEROSOL DRUG HYGROSCOPICITY WITHIN HUMAN AIRWAYS IV SUMMARY 3 USE OF MATHEMATICAL AEROSOL DEPOSITION MODELS IN PREDICTING THE DISTRIBUTION OF INHALED THERAPEUTIC AEROSOLS II HISTORICAL REVIEW OF RESPIRATORY TRACT DEPOSITION MODELS III NCRP LUNG-DEPOSITION MODEL IV ICRP LUNG-DEPOSITION MODEL V GENERAL FEATURES OF DEPOSITION MODELS VI A MULTIPLE-PATH PARTICLE DOSIMETRY MODEL VII AEROSOL SAMPLING CONVENTIONS RELATED TO RESPIRATORY DEPOSITION VIII SPECIAL FEATURES OF THERAPEUTIC AEROSOLS IX FUTURE DEVELOPMENTS IN DEPOSITION MODELING: A MODEL FOR THERAPEUTIC AEROSOLS? X SUMMARY AND CONCLUSIONS PART II: BIOLOGICAL CONSIDERATIONS 4 PHYSIOLOGY AND PHARMACOLOGY OF THE AIRWAYS II PHYSIOLOGY OF THE LUNG III PHARMACOLOGY OF THE AIRWAYS 5 SOLUTE TRANSPORT FOLLOWING AEROSOL DEPOSITION IN THE LUNGS II RADIOAEROSOLS III FACTORS AFFECTING CLEARANCE OF SOLUTES FROM THE LUNGS IV LIPID SOLUBILITY V ELECTROLYTE TRANSPORT VI STRONG ACIDS VII WATER TRANSPORT VIII REDOX INDICATORS IX MACROMOLECULES X EXHALED BREATH CONDENSATES XI CONCLUSIONS 6 DRUG METABOLISM AND ENZYME KINETICS IN THE LUNG II ENZYMATIC SYSTEMS AND THEIR DISTRIBUTION IN THE RESPIRATORY TRACT III GROSS ANATOMICAL CONSIDERATIONS IN AEROSOL DRUG DELIVERY IV EXPERIMENTAL MODELS IN LUNG METABOLISM STUDIES V CURRENT APPLICATION OF AEROSOLS IN DRUG THERAPY VI CONCLUSIONS 7 BIOAVAILABILITY AND PHARMACOKINETICS OF INHALED DRUGS II FORMULATION EFFECTS AND BIOAVAILABILITY III FACTORS AFFECTING BIOAVAILABILITY OF INHALED DRUGS IV PHARMACOKINETICS OF INHALED DRUGS V CLINICAL AND REGULATORY ISSUES VI EPILOGUE VII CONCLUSIONS 8 THERAPEUTIC USES OF LUNG AEROSOL II SYSTEMIC ROUTES OF MEDICATION DELIVERY FOR ASTHMA AND OTHER LOWER RESPIRATORY DISORDERS III AEROSOLIZED USE OF DRUGS IN ASTHMA THERAPY IV CYSTIC FIBROSIS V GENE THERAPY PART III: PHARMACEUTICS AND PHARMACEUTICAL TECHNOLOGY 9 ATOMIZATION AND NEBULIZERS II ATOMIZATION III NEBULIZERS IV FORMULATION V SUMMARY AND CONCLUSIONS 10 ULTRASONIC AND ELECTROHYDRODYNAMIC METHODS FOR AEROSOL GENERATION II ULTRASONIC NEBULIZERS III ELECTROHYDRODYNAMIC ATOMIZATION IV CONCLUSIONS 11 SPRAY-DRYING AND SUPERCRITICAL FLUID PARTICLE GENERATION TECHNIQUES I BACKGROUND II SPRAY DRYING III PARTICLE GENERATION USING SUPERCRITICAL FLUIDS IV PROPERTIES OF SPRAY-DRIED AND SCF POWDERS AND METHODS OF CHARACTERIZATION 12 INTERFACIAL PHENOMENA AND PHASE BEHAVIOR IN METERED DOSE INHALER FORMULATIONS I NOMENCLATURE II INTRODUCTION III ESTIMATING SUSPENSION STABILITY IV PROPELLANT PHYSICAL PROPERTIES AND PHASE BEHAVIOR V EXPERIMENTAL DESIGN AND METHODS VI SUMMARY AND CONCLUSIONS 13 MOLECULAR SCALE BEHAVIOR IN ALTERNATIVE PROPELLANT-BASED INHALER FORMULATIONS LIBO WU, ROBSON P S PEGUIN, PARTHIBAN SELVAM, UDAYAN CHOKSHI, AND SANDRO R P DA ROCHA I INTRODUCTION II ALTERNATIVE PMDIS III MICROSCOPIC TOOLS FOR THE DEVELOPMENT OF ALTERNATIVE PMDIS IV CONCLUSIONS AND OUTLOOK 14 AEROSOL GENERATION FROM PROPELLANT-DRIVEN METERED DOSE INHALERS II OBSERVED DROPLET FORMATION AND DISPERSION III FUNDAMENTALS OF DROPLET FORMATION IV THEORETICAL FRAMEWORK DESCRIBING DROPLET FORMATION V SEMIEMPIRICAL MODEL OF DROPLET FORMATION VI CONCLUSION 15 MEDICAL DEVICES FOR THE DELIVERY OF THERAPEUTIC AEROSOLS TO THE LUNGS II PRESSURIZED METERED-DOSE INHALERS III DRY POWDER INHALERS IV NEBULIZERS V SELECTION OF A DELIVERY SYSTEM VI FUTURE DEVELOPMENTS 16 NEXT GENERATION DRY POWDER INHALATION DELIVERY SYSTEMS II FORMULATION III METERING SYSTEMS IV DISPERSION MECHANISMS V INHALER DESIGNS (PATENT REVIEW) VI CHARACTERIZATION OF DRY-POWDER INHALER PRODUCTS VIII GENERAL CONCLUSION