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Ophthalmic Drug Delivery Systems - part 10 ppt

Ophthalmic Drug Delivery Systems - part 10 ppt

Ophthalmic Drug Delivery Systems - part 10 ppt

... pharmaceu-tical drug product will be essential.The commercial consideration for development of an ophthalmic drug delivery system is not limited to new therapeutic agents. Many existing ophthalmic drugs ... will vary with the particular dru g and the novelty ofthe particular delivery system. The approach of one company in establishingthe safety/toxicity profile of ophthalmic drugs and devices has ... analytical procedures must be specified to ana-lyze routinely the identity and purity of the drug. If the drug is in an of - cial pharmacopeia, the monograph for the drug may be referenced;however, the...
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Ophthalmic Drug Delivery Systems - part 1 pptx

Ophthalmic Drug Delivery Systems - part 1 pptx

... of a series of 50-ester prodrugs of 5-iodo-20-deoxyuridine. Pharm.Res. 5:734–737, 1988. 10 Macha et al.Copyright © 2003 Marcel Dekker, Inc. Ophthalmic Drug Delivery Systems Second Edition, ... effective ophthalmic drug delivery systems, but the knowledge in this field is rapidlyexpanding. Systems range from simple solutions to novel delivery systems such as biodegradable polymeric systems, ... Brittam96 Freeze-Drymg/Lyophilization of Pharmaceutical and Biological Prod-ucts, edited by Louis Rey and Joan C May97. Percutaneous Absorption- Drugs-Cosmetics-Mechanisms-Metho-dology,...
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Ophthalmic Drug Delivery Systems - part 10 ppsx

Ophthalmic Drug Delivery Systems - part 10 ppsx

... pharmaceu-tical drug product will be essential.The commercial consideration for development of an ophthalmic drug delivery system is not limited to new therapeutic agents. Many existing ophthalmic drugs ... activity of phosphorothio-ate antisense oligonucleotides. Mol. Pharmacol. 41 :102 3 103 3.180. O. Zelphati and F. C. Szoka, Jr. (1996). Intracellular distribution and mechan-ism of delivery of oligonucleotides ... liposomes and antisense oligonucleotide delivery. Drug Delivery, 3:67–73.192. C. Y. Wang and L. Huang. (1989). Highly efficient DNA delivery mediated bypH-sensitive immunoliposomes. Biochemistry,...
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Ophthalmic Drug Delivery Systems - part 2 pdf

Ophthalmic Drug Delivery Systems - part 2 pdf

... Ocularpharmacokineticsincludesthefeaturesofabsorption,distribu-tion,andexcretionfoundwithsystemicadministrationbutappliedtotheeye.However,owingtotheuniqueanatomyandphysiologyoftheeyeandsurroundingtissue,ocularpharmacokineticsisconsiderablymoredifficulttodescribeandpredictthanitssystemiccounterpart.Thetaskisfurthercomplicatedbythevariousformulations,routes,anddosingregimenstypi-callyencounteredinophthalmology.Pharmacodynamicsisthemeasurementofpharmacologicalresponserelativetodoseorconcentration.Thepharmacologicalresponseinducedbyadrugcanvarygreatlyfromindividualtoindividualduetodifferencesinfactorssuchaseyepigmentation,thepathologicalstateoftheeye,tearing,orblinkrate.Theapplicationofpharmacologicalendpointsisparticularlyusefulinthestudyofdrugsinthehumaneye,wheretheabilitytodeterminetheocularpharmacokineticsbasedonoculartissueconcentrationsisseverelylimited.Thischapterdiscussestheocularpharmacokineticsassociatedwithtopicalocular,intravitreal,periocular,andsystemicadministration.Inaddi-tion,thepharmacodynamicsrelatedtoophthalmicdrugsandtheroleofoculardrugmetabolismarereviewed.II.OCULARPHARMACOKINETICSApplicationofclassicalpharmacokineticstoophthalmicdrugsisprob-lematicbecauseofthecomplexitiesassociatedwitheyeanatomyandphy-siology.Asaresult,mostoftheliteratureislimitedtomeasuringconcentrationsinoculartissuesovertimefollowingsingleormultipleadministration.Thisapproach,whileinformative,doesnoteasilyyieldquantitativepredictionsforchangesinformulationordosageregimen.Compoundingtheproblemisthefactthatmoststudieshavebeenconductedinrabbiteyes,whichdiffersignificantlyfromhumaneyesinanatomyandphysiology(seeTable1).themostobviousdifferencesareinblink ... pro- drug and the subsequent hydrolysis of the prodrug to active compound (16,99 ,100 ). Prodrugs of pilocarpine (101 ), phenylephrine (102 ,103 ), timolol (104 ), and prostaglandin F2tromethamine have ... littlefromdrugto drug, asshowninTable7 in terms of half-life. The half-lives fall within arelatively narrow range of about 0.3–6 hours for a wide variety of drugs.Determining the aqueous humor half-life...
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Ophthalmic Drug Delivery Systems - part 4 doc

Ophthalmic Drug Delivery Systems - part 4 doc

... of compounds, including fluorescein (2:6 Â 10 À5cm/s), fluor-escein glucuronide (4:5 Â 10 À7cm/s), and dexamethasone sodium m-sulfo-benzoate (4:9 Â 10 À5cm/s) (1,9,15–17,30). All of the reported ... injection,increased as the drug diffusivity was reduced. Furthermore, the rate of drug elimination, which is inversely related to the drug s elimination half-life, decreased significantly as the drug diffusivity ... humor (10, 11). Thepressure-independent flow pathway behaves like a constant-rate pump;however, no metabolically dependent process has been identified as a driv-ing force for pressure-independent...
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Ophthalmic Drug Delivery Systems - part 6 docx

Ophthalmic Drug Delivery Systems - part 6 docx

... of drugs in perspective vis-a-vis ocular drug delivery. First, the noncorneal penetration pathway involves the per-meation of drug across the conjunctiva and sclera and may contribute sig-nificantly ... and Ganiban, G. J. (1995). Delivery systems for intraocularroutes, Adv. Drug Delivery Rev., 16 :107 –123.129. Geroski, D. H., and Edelhauser, H. F. (2000). Review: Drug delivery forposterior segment ... (1995). Review: Delivery systems forintraocular routes, Adv. Drug Delivery Rev., 16 :107 –123.132. Velez, G., and Whitcup, S. M. (1999). New developments in sustained release drug delivery for the...
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Ophthalmic Drug Delivery Systems - part 8 docx

Ophthalmic Drug Delivery Systems - part 8 docx

... H.(1983). Vasopressin effects on isolated non-pregnant myometrium and uterinearteries and their inhibition by deamino-ethyl-lysine-vasopressin and dea-mino-ethyl-oxytocin, Br. J. Obstet. Gynaecol., ... nearfuture. We hope that novel drug delivery systems will be developed todeliver potent polypeptide drugs through the ocular route.REFERENCES1. Lee, V. H. L. (1987). Ophthalmic delivery of peptides ... Atursson, P. (1990). Absorption of vasopressin analogue, 1- desamino-8-D-arginine-vasopressin (dDAVP), in human intestinal epithelialcell line, CaCO-2, Int. J. Pharm., 64:181.43. Amidon, G. L., Sinko,...
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Ophthalmic Drug Delivery Systems - part 9 pot

Ophthalmic Drug Delivery Systems - part 9 pot

... adenovirus encoding brain-derived neurotrophic factor (Ad-BDNF) coinjected with a free radical scavenger, N-tert-butyl-(2-sulfoph-enyl)-nitrone (S-PBN), resulted in the survival of 63% axotomized ... Phosphorothioate-modified oli-godeoxyribonucleotides, III. NMR and UV spectroscopic studies of the Rp-Rp, Sp-SP, and Rp-Sp duplexes, [d(GGSAATTCC)]2, derived from diaster-eomeric O-ethyl phosphorothioates. ... Inc.2.GeneGunGeneguntransferofDNAhasbeensuccessfullyusedinplant,microbial,andmammaliancells(61).Inadditiontotheadvantageofnonimmunogeni-city,italsoprovidesgoodinvivogenetransferefficiencyandfocalgene delivery. Theprocessinvolvespenetrationofgold-coatedDNAparticlesintothetargetorganusinganelectricarcgeneratedbyhigh-voltagedis-chargethatacceleratesDNA-coatedparticlestohighvelocity(62).PlasmidDNAencodingnontoxicgreenfluorescentproteinwasdeliveredinrabbitcornea,andtherewasnoevidenceofcornealoroculardamage(63).IthasalsobeenshownthattheballistictransferofgenesforIL-4andCTLA-4inorthotopiccornealgraftinginBALB/cmicecausedprolongedgeneexpres-sionfor5days(64).Invitro,geneexpressingcorneaspecifickeratin12proteininTantigentransformedrabbitcornealepithelium(65).Sincethetargettissueistobesurgicallyexposed,thistechniquecanbeappliedtothesurfaceoftheeyeonly.3.LiposomesLiposomesaresphericalparticlescomposedofalipidbilayermembranethatencapsulatesapartofthesolvent.Dependingonthenatureoftheconcentriclayers,theyaredesignatedSUV(smallunilamellarvesicle;0.02–0:2m),LUV(largeunilamellarvesicle;0.1–0:5m),andLMV(largemultilamellarvesicle,0.1 10 m).Thesurfacecharacteristicsoflipo-somescanbemadeneutral,negative,orpositivelychargeddependingonthenatureoftheligandsonthesurface.Anumberoflipidshavebeenstudiedfordeliveryofgenetherapyproducts,butnosingletypehasbeenidentifiedasthemostsuitableforalltypesofgenedelivery(66).Theuseofplasmid-basedgeneexpressionislimitedbytheirsize(about3000kDa),hydrophi-licity,andalargenegativesurfacecharge(À30toÀ70mV)(67).Thesepropertiesinfluencethedistributioninthetissues,cellularuptake,andintra-cellulartraffickingofgenetherapydrugs(68).Itisnowacceptedthatcatio-niclipidsarenecessaryfordevelopmentofaliposomalformulationforgenetherapybecausethenegativechargeisahindrancetocellmembranetrans-port(69,70).Thenatureofthehydrophilicandhydrophobicpartsandthelinkersplaysanimportantrole,althoughthestructure-functionrelation-shipshavenotbeenestablished.Ontheotherhand,cationiclipids(Table2)cannotformliposomesaloneandarenormallyaccompaniedbyaneutrallipid...
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