Physiological Pharmaceutics

xivContents9. Nasal Drug Delivery ................................................................................................... 199ANATOMY AND PHYSIOLOGY ....................................................................................... 200Nasal epithelia ............................................................................................................. 201Nasal lymphatic system ............................................................................................... 202Nasal secretions ........................................................................................................... 202The nasal cycle ............................................................................................................ 203Mucociliary clearance of inhaled particles .................................................................. 203Pathological effects on mucociliary function............................................................... 204External factors affecting mucociliary clearance ......................................................... 206Chemical-induced changes ........................................................................................... 207INTRANASAL ADMINISTRATION OF DRUGS ............................................................... 208Drugs administered for local action ............................................................................ 208Drugs administered for systemic effect ........................................................................ 209DRUG DELIVERY SYSTEMS AND DEPOSITION PATTERNS ........................................ 210Mechanisms to increase nasal residence time of formulations ................................... 212Excipient and drug effects on clearance ...................................................................... 213Effect of formulation pH ............................................................................................. 214INTERSPECIES COMPARISONS ........................................................................................ 216CONCLUSIONS ................................................................................................................... 216REFERENCES ....................................................................................................................... 21710. Pulmonary Drug Delivery ......................................................................................... 221STRUCTURE AND FUNCTION OF THE PULMONARY SYSTEM ................................. 222The lung ....................................................................................................................... 222Upper airway ............................................................................................................... 222Structure of the tracheo-bronchial tree ....................................................................... 223Epithelium .................................................................................................................... 225Lung permeability ........................................................................................................ 227Lung mucus ................................................................................................................. 227Lung defenses .............................................................................................................. 228Lung surfactant ............................................................................................................ 228Blood supply ................................................................................................................ 229Lymphatic system ......................................................................................................... 229Nervous control ........................................................................................................... 229Biochemical processes which occur in the lung .......................................................... 230Breathing ...................................................................................................................... 230Respiratory disease ...................................................................................................... 230DOSAGE FORMS FOR PULMONARY DRUG DELIVERY .............................................. 232Pressurized inhalation aerosols .................................................................................... 232Dry powder inhalers .................................................................................................... 234Nebulizers .................................................................................................................... 235Spacer devices and ancillary equipment ...................................................................... 236ASSESSMENT OF DEPOSITION BY GAMMA SCINTIGRAPHY .................................... 237Choice of radiolabel .................................................................................................... 237Labeling inhalation formulations ................................................................................ 238Labeling dry powder inhalers ...................................................................................... 239Validation ..................................................................................................................... 239FACTORS AFFECTING PARTICLE DEPOSITION IN THE LUNG ................................. 239Physicochemical properties .......................................................................................... 239Deposition patterns from different dose forms ........................................................... 241Physiological variables ................................................................................................. 241DRUG ABSORPTION .......................................................................................................... 242PHARMACOKINETICS ....................................................................................................... 243DRUGS ADMINISTERED VIA THE PULMONARY ROUTE ........................................... 243Anti-allergy agents ....................................................................................................... 243Beta receptor agonists .................................................................................................. 243