Physiological Pharmaceutics

Contentsxiii7. Drug Delivery to the Large Intestine and Rectum ...................................................... 143INTRODUCTION ................................................................................................................ 144ANATOMY AND PHYSIOLOGY OF THE COLON ........................................................ 144Interspecies differences in structure ............................................................................. 145Colonic structure ......................................................................................................... 146Gut wall metabolism ................................................................................................... 147Blood supply ................................................................................................................ 147Nervous and humoral control ..................................................................................... 148Colonic environment ................................................................................................... 149Colonic motility ........................................................................................................... 151Drug absorption from the colon ................................................................................. 157DRUG DELIVERY ................................................................................................................ 157Transit .......................................................................................................................... 158Dietary factors ............................................................................................................. 161Temporal factors .......................................................................................................... 161Targeting the proximal colon ...................................................................................... 161Effect of disease and co-medication on colonic drug absorption ............................... 165RECTAL ADMINISTRATION OF DRUGS ......................................................................... 166Drug absorption and avoidance of first-pass metabolism ........................................... 166Dosage forms for rectal delivery ................................................................................. 167Adjuvants and enhancers ............................................................................................. 167Spreading of rectal dosage forms ................................................................................ 168Therapeutic agents administered rectally .................................................................... 169Rectal irritation and damage ....................................................................................... 173CONCLUSIONS ................................................................................................................... 174REFERENCES ....................................................................................................................... 1748. Transdermal Drug Delivery ........................................................................................ 181INTRODUCTION ................................................................................................................ 182STRUCTURE OF THE SKIN ............................................................................................... 182Epidermis ..................................................................................................................... 183Dermis .......................................................................................................................... 184Subcutaneous fat layer ................................................................................................. 184Hair and nails .............................................................................................................. 184Sebaceous glands ......................................................................................................... 185Eccrine sweat glands .................................................................................................... 185Surface characteristics .................................................................................................. 185PASSAGE OF DRUG THROUGH THE SKIN .................................................................... 185Model systems for skin................................................................................................ 185Routes of absorption ................................................................................................... 186Advantages and disadvantages of transdermal delivery .............................................. 187FACTORS AFFECTING PERCUTANEOUS ABSORPTION ............................................... 188Individual variation ..................................................................................................... 188Age ............................................................................................................................... 188Site ............................................................................................................................... 188Occlusion ..................................................................................................................... 188Temperature ................................................................................................................. 188Race ............................................................................................................................. 189Disease ......................................................................................................................... 189VEHICLES AND DEVICES .................................................................................................. 189PENETRATION ENHANCERS ........................................................................................... 191IONTOPHORESIS ................................................................................................................ 192ELECTROPORATION ......................................................................................................... 193SONOPHORESIS .................................................................................................................. 194CONCLUSIONS ................................................................................................................... 194REFERENCES ....................................................................................................................... 195