藥劑學(xué)英文重點(diǎn)

緒論

LWhatispha門(mén)naceutics?Howmanybranchesofpha門(mén)naccutics?

2.Whatisadrug?Givesemeexamples

Adrugisdefinedasanagentintendedforuseinthediagnosis,mitigation,treatment,cure,orpreventionof

diseaseinhumansorinotheranimals.

藥物是有目的地用于診斷、緩解、治療、治愈或預(yù)防人類(lèi)或動(dòng)物疾病的物質(zhì)。

?Emetic(inducevomiting催吐齊(j)andantiemetic(preventvomiting止吐齊！J)drugs

?Diureticdrugs(increasetheflowofurine利尿劑)

?Expectorantdrugs(increaserespiratorytractfluid除痰劑)

?Catharticsorlaxatives(evacuatethebowel瀉藥)

?Otherdrugsdecreasetheflowofurine,diminishbodysecretions,orinduceconstipation(便秘)

3.Wheredonewdrugscomefrom?Giveexamples.

Newdrugsmaybederivedfrom

?Plant

?Animalsources

?Asbyproductsofmicrobialgrowth

?Throughchemicalsynthesis

?Molecularmodification

?Biotechnology

4.Explain:drugstandards,uhannacoDeia,ISO

Drugstandards

?Theunitedstatespharmacopeia(藥典)andthenationalformulary(國(guó)家藥品標(biāo)準(zhǔn))

?Pharmakon,meaning“drug”;poiein,meaning"make”;

?Thecombinationindicatesanyrecipeorformulaorotherstandardsrequiredtomakeorprepareadrug.

?Organizedsetsofmonographsorbooksofthesestandardsarecalledpharmacopeiasorformularies.

InternationalOrganizationforstandardization(ISO)

isaninternationalconsortiumofrepresentativebodiesconstitutedtodevelopandpromoteuniformor

harmonizedinternationalstandards.

國(guó)際標(biāo)準(zhǔn)化組織是一個(gè)代表性的國(guó)際聯(lián)合會(huì)，其設(shè)立是為了發(fā)展和增進(jìn)國(guó)際標(biāo)準(zhǔn)的均一性和協(xié)調(diào)性。

ISO9000-IS09004usedinthepharmaceuticalindustry

?ISOincludedstandardspertainingtodevelopment,production,qualityassurance,qualitycontrol,detection

ofdefectiveproducts,qualitymanagement,andotherissuesasproductsafetyandliability.

?ISO包括標(biāo)準(zhǔn)適合開(kāi)發(fā)、生產(chǎn)、質(zhì)量保證、質(zhì)量控制、缺陷產(chǎn)品的檢測(cè)、質(zhì)量管理和其他如產(chǎn)品安

全性和責(zé)任的問(wèn)題。

?Internationallyrecognizedquality-managementsystem.

5.Howdoyouunderstandyourroleasaclinicalpharmacist?

?Communitypharmacies

Pharmacistplaysanactiveroleinthepatient,suseofprescriptionandnonprescriptionmedication,

diagnosticagents,

durablemedicalequipmentanddevices,

otherhealth-relatedproducts.

?Patient-careinstitutions

1）Managedrugdistributionandcontrolsystems

2）Provideavarietyofclinicalservicesas

drugutilizationreviews,

druguseevaluations,

therapeuticdrugmonitoring,（治療藥物的監(jiān)測(cè)）

intravenousadmixtureprograms（靜脈藥物再己置方案）

pharmacokineticconsultservice,

investigationaldrugsupplies,

poisoncontrol,

druginformation.

?Managedcare

?Homehealthcare

?Militaryandgovernmentservice

?Academicsettings

?Professionalassociations

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Pharmaceuticalresearchandmanufacturingindustry

Themissionofthepharmacististoprovidepharmaceuticalcare.Pharmaceuticalcareisthedirect,responsible

provisionofmedication-relatedcareforthepurposeofachievingdefiniteoutcomesthatimproveapatient's

qualityoflife.

藥師的使命是提供藥學(xué)服務(wù)。藥學(xué)服務(wù)是藥物治療有關(guān)服務(wù)的直接的、責(zé)任性的提供，目的是達(dá)到增進(jìn)

患者生活質(zhì)量的明確的結(jié)果。

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4

新藥發(fā)展和審批進(jìn)程

1（思知）Describethemethodsofdrugdiscovery

?Mostdrugsaretheresultofcarefullydesignedresearchprogramsofscreening,molecularmodification,and

mechanism-baseddrugdesign.（大多數(shù)藥物是精心設(shè)計(jì)的研究過(guò)程的結(jié)果，包括：篩選、分子修飾和

基于機(jī)制的藥物設(shè)計(jì)。）

?Todetectandevaluatebiologicalactivity,bioassaysareusedtodifferentiatetheeffectandpotencyofthe

testagentcomparedwithcontrolsofknownactionandeffect.（Invitro—cellculture/Invivo

Disease-specificanimalmodels）

?Newmethods,ashighthroughputscreening,arecapableofexamining15000chemicalcompoundsaweek

using10-20biologicalassays.

■High-throughputscreening（HTS）isamethodforscientificexperimentationespeciallyusedindrug

discoveryandrelevanttothefieldsofbiologyandchemistry.

?Tobeeffective,thisrequiresasizeableandchemicallydiversecollectionofcompoundstoexamine,which

manypharmaceuticalandchemicalcompanieshaveinuchemicallibraries.,,（為了有效地利用它，這需

要有相當(dāng)大量的不同化學(xué)物質(zhì)來(lái)測(cè)試，通常許多制藥公司或化學(xué)品公司有“化合物庫(kù)”）

?Molecularmodificationinvolvesthechemicalalterationofaknownandpreviouslycharacterizedorganic

compoundforthepurposeofenhancingitsusefulnessasadrug.（分子修飾涉及化學(xué)改變已知和特性明

了的有機(jī)化合物以改善其作為藥物的有效性。）

2（思）Definethefollowingphrases:

（1）Prodm&s

isatermusedtodescribeacompoundthatrequiresmetabolicbiotransformationafteradministrationtoproduce

thedesiredpharmacologicallyactivecompound.

（前體藥物使之能夠在給藥后經(jīng)體內(nèi)代謝性生物轉(zhuǎn)化成具有期望的藥理活性化合物的化合物。）

（2）aleadcompound

isaprototype（原形化學(xué)物質(zhì)）chemicalcompoundthathasafundamentaldesiredbiologicorpharmacologic

activity.

（先導(dǎo)化合物是一種具有生物學(xué)和藥理學(xué)活性基本要求的原型化學(xué)物質(zhì)。）

（3）agoaldrug

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Intheory,a“goaldrug”

?wouldproducethespecificallydesiredeffect,

?beadministeredbythemostdesiredroute（generallyorally）atminimaldosageanddosingfrequency,

?haveoptimalonsetanddurationofactivity,

理論匕目標(biāo)藥物應(yīng)能通過(guò)最理想的途徑（通常為口服）以最小的劑量和給藥頻率給藥，能產(chǎn)生特

異的期望療效，具有最理想的起效和持續(xù)時(shí)間，

?exhibitnosideeffects,

?followingitsdesiredeffectwouldbeeliminatedfromthebodyefficiently,completely,andwithoutresidual

effect.

?itwouldbeeasilyproducedatlowcost,

?bepharmaceuticallyelegant,

?physicallyandchemicallystableundervariousconditionsofuseandstorage.

?（無(wú)副作用，并在發(fā)揮療效后能完全有效地從體內(nèi)消除，且無(wú)殘留效應(yīng)。它應(yīng)該易于生產(chǎn)，費(fèi)用低,

制劑產(chǎn)品美觀，在不同的使用和貯藏條件下物理和化學(xué)上穩(wěn)定。）

3（思）Whatphysicalandchemicalpropertiesofdrugsubstancesmustbecharacterizedduring

prefonmilationstudies?Explain.

Eachdrugsubstancehasintrinsicchemicalandphysicalcharacteristicsthatmustbeconsideredbeforethe

developmentofapharmaceuticalformulation.

①Drugsolubility

?Adrugsubstanceadministeredbyanyroutemustpossesssomeaqueoussolubilityforsystemicabsorption

andtherapeuticresponse.

?Poorlysolublecompounds（lessthanlOmg/ml）mayexhibiteitherincompleteorerratic（不穩(wěn)定）

absorptionandthusproduceaminimalresponseatdesireddosage.

②Partitioncoefficient

Toproduceapharmacologicresponse,adrugmoleculemustfirstcrossabiologicmembraneofproteinandlipid,

whichactsasalipophilicbarriertomanydrugs.

③Dissolutionrate

?Therateatwhichadrugsubstancedissolvesinamediumiscalleditsdissolutionrate.

?Dissolutionratedata,whenconsideredalongwithdataonadrug'ssolubility,dissolutionconstant,and

partitioncoefficient,canprovideanindicationofthedrug*sabsorptionpotentialfollowingadministration.

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④Physicalform

Thecrystaloramorphousformsandparticlesizeofapowdereddrugcanaffectthedissolutionrate,andthusthe

rateandextentofabsorption,foranumberofdrugs.

⑤Stability

Thechemicalandphysicalstabilityofadrugsubstancealone,andwhencombinedwithformulationcomponents,

iscriticalinpreparingasuccessfulpharmaceuticalproduct.

4（思）Whatbiologicaldiaracterizationshouldbestudiedindmgdevelopmentprocess?

?Pharmacology

?Drugmetabolism

?Toxicology

5（知）

?Pharmacodynamicsisthestudyofthebiochemicalandphysiologicaleffectsofdrugsandtheirmechanisms

ofaction.

?Pharmacokineticsdealswiththeabsorption,distribution,metabolismorbiotransformation,andexcretionof

drugs.

?Clinicalpharmacologyappliespharmacologicprinciplestothestudyoftheeffectsandactionsofdrugsin

humans.

6（知）Thescheduleofdosa*orthedosageregimen,

isdeterminedduringtheclinicalinvestigationandisbasedlargelyonadrug'sinherentdurationofaction,its

pharmacokinetics,andthecharacteristicsofthedosageform.

AtreatmentIND

oratreatmentprotocolpermitstheuseofaninvestigationaldruginthetrentmentofpatientsnotenrolledinthe

clinicalstudybutwhohaveaseriousorimmediatelylife-threateningdiseaseforwhichthereisnonsatisfactory

alternativetherapy.

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3.DosageFormDesign:PharmaceuticandFormulationConsiderations

1藥劑學(xué)定義

Thegeneralareaofstudyconcernedwiththe

formulation

manufacture

stability

effectiveness

ofpharmaceuticaldosageformsistermedpharmaceutics.

2Theneedfordosageforms

Besidesprovidingthemechanismforthesafeandconvenientdeliveryofaccuratedosage,dosageformsare

neededforadditionalreasons:

1)Toprotectthedrugsubstancefromthedestructiveinfluencesofatmosphericoxygenorhumidity(coated

tablets,sealedampuls)

2)Toprotectthedrugsubstancefromthedestructiveinfluenceofgastricacidafteroraladministration

(enteric-coatedtablets)

3)Toconcealthebitter,salty,oroffensivetasteorodorofadrugsubstance(capsules,coatedtablets,flavored

syrups)

4)ToprovideLiquidpreparationofsubstancesthatare

insoluble

orunstable

inthedesiredvehiclefSuspensions

5)Toprovideclearliquiddosageformsofsubstances,suchas-SyrupsSolutions

6)Toproviderate-controlleddrugaction(variouscontrolled-releasetablets,capsulesandsuspensions)

7)Toprovidetopicaldrugactionfromtopicaladministrationsites(ointments,creams,transdermalpatches,

ophthalmic,ear,andnasalpreparations)

8)Toprovidefortheinsertionofadrugintooneofthebody*sorifices(e.g.,rectalorvaginalsuppositories)

9)Toprovidefortheplacementofdrugsdirectlyintothebloodstreamorintobody*stissues(e.g.,injections)

10)Toprovidefortopicaldrugactionthroughinhalationtherapy(e.g.,inhalantsandinhalationaerosols)

3（知公式）

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Inthedissolutionofparticlesofdrug,thedissolvedmoleculesdiffuseawayfromtheindividualparticlebody.An

expressiontodescribethiswasderivedfromFick'sequationsandisknownastheNoyesandWhitney

expression.Itcanbewrittenasfollows:

dC/dt=(DS/h)(Cs?C)

whereCistheconcentrationofdrugdissolvedattimet,

Disthediffusioncoefficientofthesoluteinsolution,

Sisthesurfaceareaoftheexposedsolid

histhethicknessofthediffusionlayer

Csisthesaturationsolubilityofthedrug

k=DS/h

dc/dt=k(Cs-C)

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藥物劑型設(shè)計(jì)——生物藥劑學(xué)和藥物動(dòng)力學(xué)

1（掌）一些名詞

Biopharmaceutics

istheareaofstudyembracingtherelationshipbetweenthephysical,chemical,andbiologicalsciencesasthey

applytodrugs,dosageforms,andtodrugaction.

（生物藥劑學(xué)是圍繞物理學(xué)、化學(xué)和生物科學(xué)及它們關(guān)于藥物、劑型和藥物作用相互關(guān)系的研究領(lǐng)域。）

藥物動(dòng)力學(xué)

Theareaofstudywhichelucidatesthetimecourseofdrugconcentrationinthebloodandtissuesistermed

pharmacokinetics.

Itisthestudyofthekineticsofabsorption,distribution,metabolismandexcretion（ADME）ofdrugsandtheir

correspondingpharmacologic,therapeutic,ortoxicresponseinanimalsandman.

Pharmacokineticsalsomaybeappliedinthestudyofinteractionsbetweendrugs.

Activetransport

denotesaprocessofthesoluteordrugbeingmovedacrossthemembraneagainstaconcentrationgradient,thatis,

fromasolutionoflowerconcentrationtooneofahigherconcentrationor,ifthesoluteisanion,againstan

electrochemicalpotentialgradient

（主動(dòng)轉(zhuǎn)運(yùn)是指溶質(zhì)或藥物穿過(guò)生物膜的轉(zhuǎn)運(yùn)的過(guò)程是逆濃度梯度進(jìn)行，即從低濃度向高濃度轉(zhuǎn)運(yùn)或當(dāng)

溶質(zhì)是離子時(shí)逆電化學(xué)電勢(shì)梯度轉(zhuǎn)運(yùn)。）

endocytosis（內(nèi)吞）

Manylargemoleculesandparticlescannotentercellsviapassiveoractivemechanisms.However,somemay

enter,asyet,byaprocessknownasendocytosis（內(nèi)吞）

Inphagocytosis（吞噬）（celleating）

largeparticlessuspendedintheextracellularfluidareengulfedandeithertransportedintocellsoraredestroyed

withinthecell.Thisisaveryimportantprocessforlungphagocytesandcertainliverandspleencells.

Pinocytosis（胞飲）（celldrinking）

isasimilarprocessbutinvolvestheengulfingofliquidsorverysmallparticlesthatareinsuspensionwithinthe

extracellularfluid.

Thebioavailability

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describestherateandextenttowhichanactivedrugingredientortherapeuticmoietyisabsorbedfromadrug

productandbecomesavailableatthesiteofdrugaction.

Thebioequivalence

referstothecomparisonofbioavailabilitiesofdifferentformulations,drugproducts,orbatchesofthesamedrug

product.

Peakheight(Cmax)

concentrationisthemaximumdrugconcentrationobservedinthebloodplasmaorserumfollowingadoseof

thedrug.

Forconventionaldosageforms,astabletsandcapsules,theCmaxwillusuallyoccuratonlyasingletimepoint,

referredtoasTmax.

Timeofpeak(Tmax)

maximumlevelofdrugintheblood

Thisparameterreflectstherateofdrugabsorptionfromaformulation.Itistherateofdrugabsorptionthat

determinesthetimeneededfortheminimumeffectiveconcentrationtobereachedandthusfortheinitiationof

thedesiredpharmacologiceffect.

Areaundertheserumconcentrationtimecurve(AUC)

TheAUCofaconcentration-timeplotisconsideredrepresentativeofthetotalamountofdrugabsorbedintothe

circulationfollowingtheadministrationofasingledoseofthatdrug.

ThesmallertheAUC,thelessdrugabsorbed.

Pharmaceuticalequivalents

aredrugproductsthatcontainidenticalamountsoftheidenticalactivedrugingredient,i.e.,thesamesaltorester

ofthesametherapeuticmoiety,inidenticaldosageforms,butnotnecessarilycontainingthesameinactive

ingredients,andthatmeettheidenticalcompendialorotherapplicablestandardofidentity,strength,quality,and

purity,includingpotencyand,whereapplicable,contentuniformity,disintegrationtimes,and/ordissolutionrates.

(制劑等效指包含等量同種活性藥物成分的藥品，即：有相同治療效應(yīng)的相同鹽或酯的形式，相同劑型。

但并不一定包含相同的非活性成分，具有相同的外觀或其他相應(yīng)的性質(zhì)如規(guī)格、質(zhì)量、純度，包括效價(jià)、

含量均勻性、崩解時(shí)間和溶出速率。)

Pharmaceuticalalternatives

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aredrugproductsthatcontaintheidenticaltherapeuticmoiety,oritsprecursor,butnotnecessarilyinthesame

amountordosageformorasthesamesaltorester.Eachsuchproductindividuallymeetseithertheidenticalor

itsownrespectivecompendialorotherapplicablestandardofidentity,strength,quality,andpurity,including

potencyand,whereapplicable,contentuniformity,disintegrationtimes,and/ordissolutionrates.

(制劑替代品指含有相同治療效果的組成部分或它的前體藥物，不需要相同劑量、相同劑型、相同的鹽

或酯的形式。每種藥品符合同樣的或各自的外觀和其他相應(yīng)的性質(zhì)如規(guī)格、質(zhì)量、純度，包括效價(jià)，含

量均勻性、崩解時(shí)間和溶出速率。)

Bioequivalentdrug

productsarepharmaceuticalequivalentsorpharmaceuticalalternativeswhoserateandextentofabsorptiondo

notshowasignificantdifferencewhenadministeredatthesamemolardoseofthetherapeuticmoietyunder

similarexperimentalconditions,eithersingledoseormultipledose.

(生物等效性藥品指在相同的試驗(yàn)條件下，單次或多次給予相同治療劑量的藥物，其吸收的速率和程度沒(méi)

有顯示顯著性差異的制劑等效品或制劑替代品。)

Therapeuticequivalents

hasbeenusedtoindicatepharmaceuticalequivalentswhich,whenadministeredtothesameindividualsinthe

samedosageregimens,willprovideessentiallythesametherapeuticeffect.

Thehalf-life(Tl/2)

ofadrugdescribesthetimerequiredforadrug'sbloodorplasmaconcentrationtodecreasebyonehalf.

2(復(fù))Whataregeneralprinciplesofdrugabsootion?

Bodymembranesaregenerallyclassifiedasthreemaintypes:

?thosecomposedofseverallayersofcells,astheskin,

?thosecomposedofasinglelayerofcells,astheintestinalepithelium,

?thoseoflessthanonecellinthickness,asthemembraneofasinglecell.

Drugsarethoughttopenetratethesebiologicmembranesintwogeneralways:

1)bypassivediffusion

Passivediffusionisusedtodescribethepassageof(drug)moleculesthroughamembranewhichbehavesinertly

inthatitdoesnotactivelyparticipateintheprocess.

Drugsabsorbedaccordingtothismethodaresaidtobepassivelyabsorbed.

2)throughspecializedtransportmechanisms

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Thistypeoftransportisthoughttoinvolvemembranecomponentsthatmaybeenzymesorsomeothertypeof

agentcapableofformingacomplexwiththedrugatthesurfacemembrane,afterwhichthecomplexmoves

acrossthemembranewherethedrugisreleased,withthecarrierreturningtotheoriginalsurface.

(這種類(lèi)型的轉(zhuǎn)運(yùn)認(rèn)為需要涉及一些生物膜的成分，可能是酶或其他能與藥物在膜表面結(jié)合成復(fù)合物的

物質(zhì)。復(fù)合物能移動(dòng)到膜的另一側(cè)并釋放出藥物，載體則重新回到膜的表面。)

3(復(fù))WriteHendersoii?Hasselbalchequationandexplainit.

Thedegreeofadrug'sionizationdependsbothonthepHofthesolutioninwhichitispresentedtothebiologic

membraneandonthepKa.

Henderson-Hasselbalchequation

Foranacid：pH=pKa+logionizedconc.(salt)/unionizedconc.(acid)

Forabase:pH=pKa+logunionizedcone.(base)/ionizedconc.(salt)

4(復(fù))WhatisNoyes八Vhitne、equation?

ThedissolutionofasubstancemaybedescribedbythemodifiedNoyes-Whitneyequation:

dc/dt=kS(cs-ct)

inwhichdc/dtistherateofdissolution

kisthedissolutionrateconstant

Sisthesurfaceareaofthedissolvingsolid,

Csisthesaturationconcentrationofdruginthediffusionlayer

Ctistheconcentrationofthedruginthedissolutionmediumattimet

5(復(fù))Whatfactorscouldaffectdrugabsorption?

?increasingthesurfaceareaofthedrug,

?increasingthesolubilityofthedruginthediffusionlayer,

?factorsembodiedinthedissolutionrateconstant,k,includingtheintensityofagitationofthesolvent,

?thediffusioncoefficientofthedissolvingdrug.

1)Surfacearea

2)Crystaloramorphousdrugform

3)Saltforms

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4)Otherfactors

6(復(fù))Describetheroutesofdrugadministrationandtheircharacteristics?

1)Oralroute

Theoralrouteisconsideredthemostnatural,uncomplicated,convenient,andsafemeansofadministeringdrugs.

Disadvantages

Slowdrugresponse

Chanceofirregularabsorptionofdrugs

Theamountortypeoffoodpresentwithinthegastrointestinaltract

Thedestructionofcertaindrugsbytheacidreactionofthestomachorbygastrointestinalenzymes.

Dosageformsapplicable

Drugsareadministeredbytheoralrouteinavarietyofpharmaceuticalforms.

Themostpopulararetablets,capsules,suspensionsandvariouspharmaceuticalsolutions.

2)Rectalroute

Somedrugsareadministeredrectallyfortheirlocaleffectsandothersfortheirsystemiceffects.

Drugsgivenrectallymaybeadministeredassolutions,suppositories,orointments.

應(yīng)用范圍：

Rectaladministrationforsystemicactionmaybepreferredforthosedrugsdestroyedorinactivatedbythe

environmentsofthestomachandintestines.

Theadministrationofdrugsbytherectalroutemayalsobeindicatedwhentheoralrouteisprecludedbecause

ofvomitingorwhenthepatientisunconsciousorincapableofswallowingdrugssafetywithoutchoking.

3)Parenteralroute

Thethreeprimaryroutesofparenteraladministrationaresubcutaneous,intramuscular,andintravenousalthough

thereareotherssuchasintracardiacandintraspinal.

使用范圍：

Drugsdestroyedorinactivatedinthegastrointestinaltractortoopoorlyabsorbedtoprovidesatisfactoryresponse

maybeparenterallyadministered.

Theparenteralrouteisalsopreferredwhenrapidabsorptionisessential,asinemergencysituations.

Theparenteralrouteofadministrationisespeciallyusefulintreatingpatientswhoareuncooperative,

unconscious,orotherwiseunabletoacceptoralmedication.

Dosageformsapplicable

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Pharmaceutically,injectablepreparationsareusuallyeithersterilesuspensionorsolutionsofadrugsubstance

inwaterorinasuitablevegetableoil.

Drugsinsolutionactmorerapidlythandrugsinsuspension,withanaqueousvehicleprovidingfasteractionin

eachinstancethananoleaginousvehicle.

4）Epicutaneousroute

Drugsareadministeredtopically,orappliedtotheskin,fortheiractionatthesiteofapplicationorforsystemic

drugeffects.

Drugabsorptionviatheskinisenhanced

ifthedrugsubstanceisinsolution,

ifithasafavorablelipid/waterpartitioncoefficient,

ifitisanon-electrolyte.

5）Ocular,oral,andnasalroutes

Ophthalmicsolutionsandsuspensionsaresterileaqueouspreparationswithotherquantitiesessentialtothe

safetyandcomfortofthepatient.

Ophthalmicointmentsmustbesterile,andalsofreeofgrittiness.

7（復(fù)）Whatisbiotransformation?Whatarethebiochemicalmechanismsofbiotransformation?

Biotransformationisatermusedtoindicatethechemicalchangesthatoccurwithdrugswithinthebodyasthey

aremetabolizedandalteredbyvariousbiochemicalmechanisms.

Theprocessofbiotransformationiscommonlyreferredtoasthe“detoxification“oruinactivation“process.

Therearefourprincipalchemicalreactionsinvolvedinthemetabolismofdrugs:

oxidation

reduction

hydrolysis

conjugation

Othermetabolicprocesses,includingmethylation,andacylationconjugationreactions,occurwithcertain

drugstofosterelimination.

8（復(fù)）Explainshortlyaboutonecompartmentmodelandtwocompartmentmodel?

?Thesimplestpharmacokineticmodelisthesinglecompartmentopen-modelsystem.

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Thismodeldepictsthebodyasonecompartmentcharacterizedbyacertainvolumeofdistribution(Vd)that

remainsconstant.

?Inthetwo-compartmentsystem,adrugentersintoandisinstantaneouslydistributedthroughoutthecentral

compartment.

Itssubsequentdistributionintothesecondorperipheralcompartmentisslower.

9(復(fù))Howtodevelopdosageregimens?

Therearetwoapproachestothedevelopmentofdosageregimens:

1)Theempiricalapproach,whichinvolvestheadministrationofadruginacertainquantity,notingthe

therapeuticresponseandthenmodifyingthedosageofdrugandthedosingintervalaccordingly.

2)Thekineticapproachisbasedontheassumptionthatthetherapeuticandtoxiceffectsofadrugarerelatedto

theamountofdruginthebodyortotheplasmaconcentrationofdrugatthereceptorsite.

Throughcarefulpharmacokineticevaluationofadrug*sabsorption,distribution,metabolismandexcretionin

thebodyfromasingledose,thelevelsofdrugattainedfrommultipledosingcanbeestimated.

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5PowdersandGranules

1(復(fù))Whyisparticlesizeanalysisimportantinpharmaceuticalformulation?

Granulestypicallyfallwithintherangeof4(4.75mm)to12-sievesize,althoughgranulationsofpowders

preparedinthe12-to20-sieve(850m)rangearesometimesusedintabletmaking.

Thepurposeofparticlesizeanalysisinpharmacyistoobtainquantitativedataonthesize,distribution,and

shapesofdrugandothercomponentstobeusedinpharmaceuticalformulations.

Particlesizecaninfluenceavarietyofimportantfactors,includingthefollowing:

1)Dissolutionrateofparticlesintendedtodissolve;drugmicronizationcanincreasetherateofdrugdissolution

anditsbioavailability.

2)Suspendabilityofparticlesintendedtoremainundissolvedbutuniformlydispersedinaliquidvehicle(e.g.,

finedispersionshaveparticlesapproximately0.5-10Hm).

3)Uniformdistributionofadrugsubstanceinapowdermixtureorsoliddosageformtoensuredose-to-dose

contentuniformity.

4)Penetrabilityofparticlesintendedtobeinhaledfordepositiondeepintherespiratorytract(e.g.,1-5m).

5)Lackofgrittinessofsolidparticlesindermalointments,creams,andophthalmicpreparations(e.g.,fine

powdersmaybe50-100minsize).

2(復(fù))Howarepowdersofchemicaldniqsofficiallydefined?

Powdersofvegetableandanimaldrugsareofficiallydefinedasfollows:

?Verycoarse(No.8):AllparticlespassthroughaNo.8sieve(2.36mm)andnotmorethan20%througha

No.60sieve(250m).

?Coarse(No.20):AllparticlespassthroughaNo.20sieve(850m)andnotmorethan40%throughaNo.

60sieve.

?Moderatelycoarse(No.40):

AllparticlespassthroughaNo.40sieve(425m)andnotmorethan40%throughaNo.80sieve(180m).

?Fine(No.60):

AllparticlespassthroughaNo.60sieve(250m)andnotmorethan40%throughaNo.100sieve(150

m).

?Veryfine(oraNo.80):

AllparticlespassthroughaNo.80sieve.Thereisnolimittogreaterfineness.

19

Thepowderfinenessforchemicalsisdefinedasfollows

?Course(oraNo.20)powder-AllparticlespassthroughaNo.20sieveandnotmorethan60%throughaNo.

40sieve.

?ModeratelyCourse(oraNo.40)powder-AllparticlespassthroughaNo.40sieveandnotmorethan60%

throughaNo.60sieve.

?Fine(oraNo80)powder-AllparticlespassthroughaNo.80sieve.Thereisnolimitastogreaterfineness.

?Veryfine(oraNo.120)powder-AllparticlespassthroughaNo.120sieve.Thereisnolimitastogreater

fineness.

3(復(fù))Whatarethemethodsfordete門(mén)ninationofparticlesize?

Anumberofmethodsexistforthedeterminationofparticlesize

1)Sieving

Particlesarepassedbymechanicalshakingthroughaseriesofsievesofknownandsuccessivelysmallersizeand

thedeterminationoftheproportionofpowderpassingthroughorbeingwithheldoneachsieve(rangeabout

40-9500m,dependinguponsievesizes).

2)Microscopy

inwhichtheparticlesaresizedthroughtheuseofacalibratedgridbackgroundorothermeasuringdevice,(range

0.2100m)

3)Sedimentationrate

inwhichparticlesizeisdeterminedbymeasuringtheterminalsettlingvelocityofparticlesthroughaliquid

mediuminagravitationalorcentrifugalenvironment.(range:0.8-300microns)

4)Lightenergydiffractionorlightscattering

Inwhichparticlesizeisdeterminedbythereductioninlightreachingthesensorastheparticle,dispersedina

liquidorgas,passesthroughthesensingzone(range0.2500microns).

5)Laserholography(激光全息照相術(shù))

Inwhichapulsedlaserisfiredthroughanaerosolizedparticlesprayandphotographedinthreedimensions

withaholographiccamera,allowingtheparticlestobeindividuallyimagedandsized(range:1.4

lOOmicros)用一?束激光通過(guò)霧化粒子流，用全息照相術(shù)拍三維照片，觀察到粒子的形態(tài)和大小。

6)Cascadeimpaction(階式碰撞)

isbasedontheprinciplethataparticle,drivenbyanairstream,willimpactonasurfaceinitspath,providedthat

itsinertia(慣性)issufficienttoovercomethedragforcethattendstokeepitintheairstream.