Physiological Pharmaceutics

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Chapter ElevenOcular Drug DeliveryINTRODUCTIONSTRUCTURE OF THE EYECorneaConjunctiva and scleraChoroid and retinaAqueous humorEyelidsPrecorneal tear filmPhysical properties of tearsLacrimal drainage systemBlood-eye barriersFACTORS AFFECTING DRUG PERMEATIONIonization and pHProtein bindingPigmentation and drug effectsDrug distribution in the eyeDrug penetration through the sclera and conjunctivaFACTORS INFLUENCING DRUG RETENTIONProper placement of the eyedropsInfluence of instilled volumePreservativesEffect of systemically administered drugsROUTES OF DRUG ADMINISTRATIONTopical AdministrationDropsPerfusionSpraysUse of polymers to increase viscosityGelling polymersOintmentsParticulatesSustained release devicesIntraocular drug deliveryLiposomesMicroparticulates and nanoparticlesIntraocular devicesIontophoresisSystemic administrationCONCLUSIONSREFERENCES249
250 <strong>Physiological</strong> <strong>Pharmaceutics</strong>INTRODUCTIONThe external eye is readily accessible for drug administration. As a consequence of itsfunction as the visual apparatus, mechanisms are strongly developed for the clearance offoreign materials from the cornea to preserve visual acuity. This presents problems in thedevelopment of formulations for ophthalmic therapy.Topical administration is direct, but conventional preparations of ophthalmic drugs,such as ointments, suspensions, or solutions, are relatively inefficient as therapeutic systems.Following administration, a large proportion of the topically applied drug is immediatelydiluted in the tear film and excess fluid spills over the lid margin and the remainder is rapidlydrained into the nasolacrimal duct. A proportion of the drug is not available for immediatetherapeutic action since it binds to the surrounding extraorbital tissues. In view of theselosses, frequent topical administration is necessary to maintain adequate drug levels.Systemic administration of a drug to treat ocular disease would require a highconcentrations of circulating drug in the plasma to achieve therapeutic quantities in theaqueous humor, with the increased risk of side effects.Three important factors have to be considered when attempting drug delivery to the eye-1. how the blood-eye barrier (systemic to ocular) or cornea (external to ocular) iscrossed to reach the site of action,2. how to localize the pharmacodynamic action at the eye and minimise drug actionon other tissues3. how to prolong the duration of drug action such that the frequency of drugadministration can be reduced.Figure 11.1 Vertical section through the human eye
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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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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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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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Small intestine 131It was soon real
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Small intestine 133colonic absorpti
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Small intestine 135also transform d
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Small intestine 137REFERENCES1. Bry
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Small intestine 13949. Hidalgo IJ,
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Small intestine 14193. Bogentoft C,
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Page 268 and 269: Ocular drug delivery 251STRUCTURE O
Page 270 and 271: Ocular drug delivery 253chamber. It
Page 272 and 273: Ocular drug delivery 255The superfi
Page 274 and 275: Ocular drug delivery 257Figure 11.7
Page 276 and 277: Ocular drug delivery 259Figure 11.9
Page 278 and 279: Ocular drug delivery 261Influence o
Page 280 and 281: Ocular drug delivery 263SpraysSpray
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Page 288 and 289: Chapter TwelveVaginal and Intrauter
Page 290 and 291: Vaginal and intrauterine drug deliv
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Page 301 and 302: 284 GlossaryAntipyrine An analgesic
Page 303 and 304: 286 GlossaryClonazepam An anticonvu
Page 305 and 306: 288 GlossaryEsterase An enzyme whic
Page 307 and 308: 290 Glossaryfound in the synovial f
Page 309 and 310: 294 GlossaryPectoral muscle Chest m
Page 311 and 312: 296 Glossarysize exclusion (gel fil
Page 313 and 314: 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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