Physiological Pharmaceutics

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Chapter SevenDrug Delivery to the Large Intestineand RectumINTRODUCTIONANATOMY AND PHYSIOLOGY OF THE COLONInterspecies differences in structureColonic structureColonic mucosaMucusGut wall metabolismBlood supplyNervous and humoral controlColonic environmentWater and electrolytespHBacteriaColonic motilityPatterns of motilityElectrical activityGastrocolic reflexDefaecationPhysiological factors affecting colonic motilityThe effect of dietInfluence of drugsDrug absorption from the colonDRUG DELIVERYTransitDietary factorsTemporal factorsTargeting the proximal colonpHTimeBioadhesivesBacterially triggered systemsBacterial degradation of drugEffect of disease and co-medication on colonic drug absorptionRECTAL ADMINISTRATION OF DRUGSDrug absorption and avoidance of first-pass metabolismDosage forms for rectal deliveryAdjuvantsSpreading of rectal dosage formsTherapeutic agents administered rectallyAnticonvulsantsPreoperative medication and induction of anaesthesiaAnalgesis and antiarthritics143
144 Physiological PharmaceuticsAntiemeticsAntibacterial agentsXanthinesDrugs in inflammatory bowel diseaseCardiovascular active drugsRectal irritation and damageCONCLUSIONSREFERENCESINTRODUCTIONThe large intestine is responsible for the conservation of water and electrolytes, formationof a solid stool, and storage of faeces until a convenient time for defaecation. Its functionis quite distinct from that of the small intestine whose primary role is the digestion of foodand absorption of simple nutrients.Administration by the rectal route is preferable for drugs which produce emesis or areirritant when given orally. For the purposes of drug delivery, the colon has to be consideredas two regions; the distal colon, which can be reached from the anus, and the proximalcolon, which is only accessible via the oral route. The splenic flexure limits the area ofexposure of drugs administered by the anal route to the descending and sigmoid colon,rectum and anus. Instillation of large volumes to overcome this restriction triggers thedefaecation reflex. Nevertheless the rectal route is popular in Europe, though not in theU.S.A! Formulations targeted to the proximal colon have to be delivered via the oral routeand must be protected against the hostile environment of the stomach and small intestine.Transit through the colon is slower than other areas of the gastrointestinal tract and so thereis an opportunity for sustained drug delivery from the ascending and first part of thetransverse colon.ANATOMY AND PHYSIOLOGY OF THE COLONThe colon extends from the ileo-caecal junction to the anus and is approximately 125 cmlong in vivo. The large intestine is wider and shorter than the small intestine. The lumenprogressively diminishes from a maximum diameter at the caecum (about 8.5cm) to thesigmoid segment (about 2.5 cm). It can be divided into the caecum, ascending, transverse,descending, and sigmoid colon, rectum and anus (Figure 7.1).The caecum is the widest part of the colon and is a downward pointing blind pouchapproximately 8.5 cm long with the appendix attached to its apex, and its base at theileocaecal junction. It is attached to the floor of the right iliac fossa by the peritoneum,within the folds of which lies the appendix. It receives undigested food material from thesmall intestine and is considered the first region of the large intestine. It is separated fromthe ileum (the final portion of the small intestine) by the ileocecal valve (also called Bauhin’svalve). The ileocaecal valve limits the rate of food passage into the caecum and may helpprevent material from returning to the small intestine. In humans, the caecum’s mainfunctions are to absorb fluids and salts that remain after the completion of intestinaldigestion and absorption, and to mix its contents with mucus for lubrication. The internalwall is composed of a thick mucous membrane beneath which is a deep layer of muscletissue that produces churning and kneading motions.The ascending colon is approximately 20 cm long and extends from the caecum to thehepatic flexure, which lies lateral to the right kidney and in contact with the inferior surfaceof the liver. The transverse colon is normally over 45 cm in length and hangs loosely betweenthe hepatic and the splenic flexures, often following the greater curvature of the stomach.The splenic flexure is usually located higher than the hepatic flexure. The descending colon
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For Alexander and SarinaWith all ou
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First edition 1989Second edition fi
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viPrefacepublishers, who I am sure,
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viiiAcknowledgementsFig 6.5 is repr
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Table of Contents1. Cell Membranes,
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xiiContentsGASTRIC pH .............
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xivContents9. Nasal Drug Delivery .
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Chapter OneCell Membranes, Epitheli
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Membranes and barriers 3Figure 1.1
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Membranes and barriers 5Modulation
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Membranes and barriers 7Membrane pr
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Chapter TwoParenteral Drug Delivery
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Parenteral drug delivery 21Figure 2
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Parenteral drug delivery 23catheter
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Parenteral drug delivery 29fluid is
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Parenteral drug delivery 33Receptor
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Parenteral drug delivery 3526. Tsuj
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38 Physiological PharmaceuticsANATO
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40 Physiological PharmaceuticsFigur
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42 Physiological Pharmaceuticsgland
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44 Physiological PharmaceuticsABSOR
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58 Physiological Pharmaceutics59. A
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60 Physiological PharmaceuticsINTRO
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72 Physiological Pharmaceutics12. W
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Chapter FiveThe StomachANATOMY AND
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The stomach 77Figure 5.2 Structure
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The stomach 79Gastric glandsThe gas
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The stomach 81Figure 5.7 Mechanism
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The stomach 83absorbed from the sto
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The stomach 85Night-time transient
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The stomach 87particle size indiges
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The stomach 89Figure 5.13 MRI cross
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Page 110 and 111: The stomach 93Figure 5.15 The effec
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Page 114 and 115: The stomach 97Figure 5.17 The gastr
Page 116 and 117: The stomach 99In order to improve b
Page 118 and 119: The stomach 101Figure 5.21—Gastri
Page 120 and 121: The stomach 103The anatomy and dime
Page 122 and 123: The stomach 10533:1283-1290.35. Cun
Page 124 and 125: The stomach 10782. Ingani HM, Timme
Page 126 and 127: Chapter SixDrug Absorption from the
Page 128 and 129: Small intestine 111Figure 6.1 Secti
Page 130 and 131: Small intestine 113are uncommon and
Page 132 and 133: Small intestine 115underlying tissu
Page 134 and 135: Small intestine 117Brief periodic b
Page 136 and 137: Small intestine 119is extremely rap
Page 138 and 139: Small intestine 121Figure 6.5 Segme
Page 140 and 141: Small intestine 123Measurements of
Page 142 and 143: Small intestine 125Figure 6.8 Small
Page 144 and 145: Small intestine 127Scintigraphy oft
Page 146 and 147: Small intestine 129It is known that
Page 148 and 149: Small intestine 131It was soon real
Page 150 and 151: Small intestine 133colonic absorpti
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Page 154 and 155: Small intestine 137REFERENCES1. Bry
Page 156 and 157: Small intestine 13949. Hidalgo IJ,
Page 158: Small intestine 14193. Bogentoft C,
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222 Physiological PharmaceuticsDRUG
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Chapter ElevenOcular Drug DeliveryI
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Ocular drug delivery 251STRUCTURE O
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Ocular drug delivery 253chamber. It
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Ocular drug delivery 255The superfi
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Ocular drug delivery 257Figure 11.7
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Ocular drug delivery 259Figure 11.9
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Ocular drug delivery 261Influence o
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Ocular drug delivery 263SpraysSpray
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Ocular drug delivery 265endothelial
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Ocular drug delivery 267polymers ha
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Ocular drug delivery 269sustained-r
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Chapter TwelveVaginal and Intrauter
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Vaginal and intrauterine drug deliv
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284 GlossaryAntipyrine An analgesic
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286 GlossaryClonazepam An anticonvu
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288 GlossaryEsterase An enzyme whic
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290 Glossaryfound in the synovial f
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294 GlossaryPectoral muscle Chest m
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296 Glossarysize exclusion (gel fil
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298 GlossaryTributyrase An enzyme w
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300 Indexß-glucuronidase 276B cell
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302 IndexDiazoxide 262Dichlorodiphe
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304 IndexGelling polymers 264Gels 1
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306 IndexEpithelium 225Factors affe
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308 IndexOros ® 158Osmotic deliver
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310 IndexAbsorption 186Age 188Disea
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312 IndexDrug absorption 277Fluid 2
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