Physiological Pharmaceutics

xiiContentsGASTRIC pH .......................................................................................................................... 83Circadian rhythm of acidity .......................................................................................... 84pH and gender ............................................................................................................... 85pH and age .................................................................................................................... 85pH and smoking ............................................................................................................ 85GASTRIC MOTILITY ............................................................................................................ 85The fasted state .............................................................................................................. 85The fed state .................................................................................................................. 86Physiological factors which influence gastric emptying ................................................ 92Effect of disease on gastric emptying ............................................................................ 93DISPERSION OF DOSAGE FORMS IN THE STOMACH .................................................. 94Hard gelatin capsules .................................................................................................... 94Soft gelatin capsules ...................................................................................................... 94GASTRIC EMPTYING OF DOSAGE FORMS ..................................................................... 95Time of dosing relative to a meal ................................................................................. 98Retention of formulations in the stomach .................................................................... 98Posture effects .............................................................................................................. 101Drug-induced effects on gastric emptying ................................................................... 102GASTRIC pH AND ENTERIC COATINGS ........................................................................ 102DRUG/FORMULATION INDUCED ULCERATION .......................................................... 102ANIMAL MODELS FOR GASTRIC EMPTYING .............................................................. 103REFERENCES ....................................................................................................................... 1036. Drug Absorption from the Small IntestineANATOMY AND PHYSIOLOGY OF THE SMALL INTESTINE ..................................... 109Gross morphology ....................................................................................................... 110Mucosa ........................................................................................................................ 110Organisation of the mucosa ........................................................................................ 111The gastrointestinal circulation ................................................................................... 113The lymphatic system .................................................................................................. 114Secretions into the small intestine ............................................................................... 116Secretion and absorption of water .............................................................................. 117Digestion and absorption of nutrients ......................................................................... 118PATTERNS OF MOTILITY IN THE SMALL INTESTINE ................................................ 120Stagnation at the ileocaecal junction ........................................................................... 121SMALL INTESTINAL TRANSIT TIMES ............................................................................ 122Methods for measuring small intestinal transit ........................................................... 122Small intestinal transit times of food .......................................................................... 123Physiological and pathophysiological effects on small bowel transit ......................... 123Small intestinal transit time of dosage forms .............................................................. 124Density and small intestinal transit ............................................................................. 127ABSORPTION OF DRUGS .................................................................................................. 127Absorption and delivery of macromolecules ............................................................... 128Intestinal pH ................................................................................................................ 129Solvent drag and intestinal permeability ..................................................................... 129P-glycoprotein .............................................................................................................. 130Cytochrome P450 3A4 (CYP3A4) .............................................................................. 131Intestinal reserve length ............................................................................................... 132Interaction with food ................................................................................................... 133First-pass metabolism .................................................................................................. 134RELATIONSHIP BETWEEN DRUG ABSORPTION ANDPOSITION OF DOSE FORM ........................................................................................... 135Radio controlled capsule ............................................................................................. 135Absorption of drugs and foreign substances through the lymphatic system .............. 136DRUG INDUCED DAMAGE ............................................................................................... 136REFERENCES ....................................................................................................................... 137