Physiological Pharmaceutics

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Chapter EightTransdermal Drug DeliveryINTRODUCTIONSTRUCTURE OF THE SKINEpidermisDermisSubcutaneous fat layerHair and nailsSebaceous glandsEccrine sweat glandsSurface characteristicsPASSAGE OF DRUG THROUGH THE SKINModel systems for skinRoutes of absorptionAdvantages and disadvantages of transdermal deliveryFACTORS AFFECTING PERCUTANEOUS ABSORPTION.Individual variationAgeSiteOcclusionTemperatureRaceDiseaseVEHICLES AND DEVICESPENETRATION ENHANCERSIONTOPHORESISELECTROPORATIONSONOPHORESISCONCLUSIONSREFERENCES181
182 <strong>Physiological</strong> <strong>Pharmaceutics</strong>INTRODUCTIONThe skin, or integument, of the human body both provides protection and receives sensorystimuli from the environment. The skin is the most extensive and readily accessible organof the body. In an average adult, it covers a surface area of over 2m2 and receives about onethirdof the blood circulation; this blood drains into the venous circulation and so avoidsfirst-pass metabolism. It is normally self-regenerating.Although it is well known that drugs can be applied to the skin for local treatmentof dermatological conditions, the advantages of accessibility and the avoidance of first-passmetabolism make it attractive for the systemic delivery of drugs. The objective of atransdermal delivery system is to provide a sustained concentration of drug for absorption,without breaching the barrier function of the skin, and avoiding local irritation. However,the slow transport of many drugs across the skin limits this technique to potent drugs whichrequire plasma concentrations of only a few µg per ml.Generally, the higher the lipid solubility of a drug and the lower its melting point, thefaster it will penetrate the skin. Several drugs can be successfully administered by this route,notably scopolamine, glycerine trinitrate, clonidine and oestradiol. Nicotine patches arebecoming common in smoking cessation programs. Nonsteroidal anti-inflammatory drugs(NSAIDs) are also being administered increasingly by transdermal delivery for the treatmentof local muscle inflammation. Recently some attention has been focused on the delivery ofacetylcholinesterase inhibitors for the treatment of Alzheimer’s disease 1 . Other potentialcandidates are ß-blockers, antihistamines and testosterone.STRUCTURE OF THE SKINThe skin is elastic and quite rugged despite the fact that it is only approximately 3 mm thick.It consists of three anatomical layers, the epidermis, the dermis and a subcutaneous fat layer(Figure 8.1).Figure 8.1 Structure of the skin
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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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46 Physiological PharmaceuticsThe r
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48 Physiological Pharmaceuticsa) in
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50 Physiological Pharmaceuticswhen
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56 Physiological Pharmaceutics8. We
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58 Physiological Pharmaceutics59. A
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60 Physiological PharmaceuticsINTRO
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64 Physiological PharmaceuticsTable
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66 Physiological Pharmaceuticsliqui
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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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The stomach 91species and man is po
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The stomach 93Figure 5.15 The effec
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The stomach 95emerged from the shel
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The stomach 97Figure 5.17 The gastr
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The stomach 99In order to improve b
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The stomach 101Figure 5.21—Gastri
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The stomach 103The anatomy and dime
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The stomach 10533:1283-1290.35. Cun
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The stomach 10782. Ingani HM, Timme
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Chapter SixDrug Absorption from the
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Small intestine 111Figure 6.1 Secti
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Small intestine 113are uncommon and
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Small intestine 115underlying tissu
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Small intestine 117Brief periodic b
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Small intestine 119is extremely rap
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Small intestine 121Figure 6.5 Segme
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Small intestine 123Measurements of
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Small intestine 125Figure 6.8 Small
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Small intestine 127Scintigraphy oft
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Small intestine 129It is known that
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Page 154 and 155: Small intestine 137REFERENCES1. Bry
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Page 158: Small intestine 14193. Bogentoft C,
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246 Physiological Pharmaceutics9. P
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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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