Physiological Pharmaceutics

Table of Contents1. Cell Membranes, Epithelial Barriers and Drug Absorption............................................ 1INTRODUCTION ....................................................................................................................2THE PLASMA MEMBRANE ................................................................................................... 2The phospholipid bilayer ................................................................................................. 3Dynamic behaviour of membranes .................................................................................. 4Modulation of membrane fluidity by sterols .................................................................. 5Models of cell membranes ............................................................................................... 5Membrane proteins .......................................................................................................... 7Membrane asymmetry ..................................................................................................... 7EPITHELIA ............................................................................................................................... 7Cell junctions ................................................................................................................... 8TRANSPORT ACROSS CELL MEMBRANES ...................................................................... 12Passive diffusion ............................................................................................................ 12Facilitated and carrier mediated diffusion ..................................................................... 14Cotransport .................................................................................................................... 14Uptake of macromolecules and particles ....................................................................... 15INTERCELLULAR ROUTES OF ABSORPTION .................................................................. 16PERSORPTION ...................................................................................................................... 16MUCUS ................................................................................................................................... 17CONCLUSIONS .....................................................................................................................18REFERENCES ......................................................................................................................... 182. Parenteral Drug Delivery .............................................................................................. 19INTRODUCTION ................................................................................................ 20INTRAVENOUS DELIVERY ................................................................................ 20Physiology ..................................................................................................... 20Advantages and disadvantages of intravenous delivery................................. 21Formulation considerations........................................................................... 23Devices and technologies .............................................................................. 23Injected particulates ...................................................................................... 24Intravenous oxygen carriers .......................................................................... 25INTRAMUSCULAR DELIVERY .......................................................................... 26Physiology ..................................................................................................... 26Pharmacokinetics .......................................................................................... 26Formulation considerations........................................................................... 28SUBCUTANEOUS DELIVERY .............................................................................. 28Physiology ..................................................................................................... 28Subcutaneous colloidal delivery systems ....................................................... 29TISSUE DAMAGE AND BIOCOMPATABILITY ................................................. 29DRUG DISTRIBUTION FOLLOWING PARENTERAL ADMINISTRATION .... 30PROTEIN BINDING ............................................................................................ 31THE BLOOD-BRAIN BARRIER .......................................................................... 32Physiology ..................................................................................................... 32Uptake by diffusion ...................................................................................... 32Receptor-mediated transport ......................................................................... 33Colloidal delivery .......................................................................................... 33REFERENCES ....................................................................................................... 34x