常用藥物劑型與臨床應(yīng)用

常用藥物劑型與臨床應(yīng)DosageFormandClinicalDepartmentofXuanwuHospitalofCapitalMedicalUniversityYanSuying學(xué)習(xí)目LearningAfterlearningthisclass,thestudentwillbeableTheclinicalapplicationoforal,sustained-release,andinjection口服劑型、緩控釋劑型、注射劑臨床應(yīng)用特Explainthedifferencebetweendosageformandrouteof劑型與給藥途徑的區(qū)ClassificationandcharacteristicsofdosageThequalityoftheinjections注射劑質(zhì)量要Compareandcontrasttheadvantages/disadvantagesofvariousdrugdosageforms比較各種劑型的優(yōu)勢(shì)與劣勢(shì)DesignofdrugformsDosage 膠囊劑 片劑

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貼劑 6WhatisdrugdosageTheclassificationofdrugdosageformsand ClinicalapplicationoforaldosageformsHowtorationallyuseInjection（注射劑合理應(yīng)用NewDrugdeliverysystem（新型給藥系統(tǒng)7(ConceptsofdosageDosageformisthephysicalformof(ConceptsofdosageThereareabout40variatiesofcommondosageforms.8一、藥物劑型分類與特(classificationandcharacteristicsofdosage9classificationclassificationofdosageDependingonthemethod/routeofadministration,dosageformscomeinseveraltypes.Theseincludemanykindsofliquid,solid,andsemisoliddosageCommondosageformsincludepill,tablet,orcapsule,drinkorsyrup,andnaturalorherbalformsuchasplantorfoodofsorts,amongmanyNotably,therouteofadministration(ROA)fordrugdeliveryisdependentonthedosageformofthesubstanceinquestion.（一）Classificationbyroutesofadministration:six(按給藥途徑分六類Oraldosageforms:tablet,capsule,Powder,Solution,syrup Parenteraldosageforms:Solutionorsuspensionfor胃腸外給藥 Rectaldosageforms：enema,直腸給藥 灌腸劑、栓劑等Inhaleddosageforms:aerosol,Inhaler&MetereddoseTopicaldosageforms：cream(oil/water≈1)，ointment(oilMucosaldosageforms：eyedrops(ophthalmic),eardrops,skin ClassificationsClassificationsbypatternsThisclassificationmethodismoreusefulinThisclassificationmethodismoreusefulinthepreparation,storageandtransportationof液體劑型：Soliddosageform:granules,tablets,capsulesSemisoliddosageform:ointment,gelGasdosageform:aerosol,sprayet氣體劑型：氣霧劑、噴霧劑等（三）新給藥劑型New（三）新給藥劑型NewDrugdeliveryMicro-capsule微囊 微 transdermalplastics透皮ingdrug-deliverysystem靶向給藥系Delayed-release Oraldosage 44Mucosaldosageforms Injection注射 ApharmaceuticalApharmaceuticaldrugcanbemadeintoavarietyofApharmaceuticaldrugcanbemadeintoavarietyofVariousdosageformsmayexistforthesamedifferentmedicalconditionsmaywarrantdifferentroutesofForexample,persistentvomiting（持續(xù) ）maymakeitdifficulttouseanoraldosageform;inthiscase,itmaybeadvisabletouseeitheraninjectionorasuppository.Also,specificdosageformsmaybewarrantedforcertainmedications,sincetheremaybeproblemswithstability,e.g.insulincannotbegivenorallysinceitisdigestedbythegut.TheeffectofthedrugdosageTheeffectofthedrugdosageformsonthedrugFastacting：injections,sublingualtablet(glyceryl速效：注射劑、舌下含片（硝酸甘油Slowactingorlong-acting：sustained-releasepreparations慢效或長(zhǎng)效制劑：緩控釋制劑（硝苯地平Alteringthenatureofthedrugfunction25%magnesiumsulfateinjection（intravenousinfusion）—inhibit50%magnesiumsulfatesolutionoral—Reducingadversedrugeffectsindometacincapsulescauselargegastrointestinal吲哚美辛膠囊—indometacinsuppositoriesreducegastrointestinal吲哚美辛拴劑—TheeffectofthedrugdosageformsonthedrugPositioning ing定位和靶向作用amphotericinBliposome-mainlygatheronreticularepithelialcells，reducingkidney兩性霉素B Alteringthestabilityofthedrugpenicillinpowder>>>penicillinInfluencingthedrugNifedipine–nifedipinesuspentionToimprovepatients’medicationsustained（controlled）releasetablet緩（控）釋片transdermalplastics透皮貼藥物劑型的重要Importanceofdosage1Increased2improvethe3ReducetheadversedrugTheThepharmacokineticcharacteristicsofdifferentdosageforms(drug-timecurve)二、藥物劑型/制劑設(shè)DesignofDosageForm/PreparationandClinicalEfficacy（一）（一）DesignofDosageThefeatureofpharmacodynamicsandThephysicochemicalpropertyofThedemandofclinicalAbsorptionAbsorptioneffectsdependonthedrugdosageThefeatureofbiopharmaceutics—routesof生物藥劑學(xué)特征—給藥途生物利用RouteofAcetaminophen對(duì)乙酰氨基Oral（口服Aspirin阿司匹Oral（口服Oral口Injection肌Gentamycin慶大霉肌Gentamycin慶大霉口服(胃腸道疾病IfIfthebioavailabilityisabove0.6(60%),drugisdesignedasoral一般生物利用度在0.6（60%）以上，設(shè)計(jì)為口Ifthebioavailabilityisbelow0.3(30%),drugisdesignedasinjection生物利用度在0.3（30%）以下，設(shè)計(jì)為注射2.The2.ThephysicochemicalpropertiesofPhysicalappearance物理狀態(tài)soliddrug固體：新藥研發(fā)時(shí)，口服有效，設(shè)計(jì)考慮次序：膠囊—片劑Liquiddrug液體：softcapsuleLiposolubility脂溶性：易于透過(guò)細(xì)胞膜，口服制Thestabilityingastrointestine藥物在胃腸道中的穩(wěn)定性(digestiveenzyme消化酶gastricacid胃酸PenicillinInterferonInsulinOmeprazoleenteric-coatedUnstableinacidicenvironment.The20mgtabletdispersesrapidlyinthestomachtoreleaseabout1,000small(0.5mm)individuallyentericcoatedmicropellets.Itcannotbechewedorground.Itissolubleinwaterorweakacidicsolution(juice),takenwithin30mins.酸性環(huán)境不穩(wěn)定，由腸溶衣微丸組成。每片20毫克口服片劑中大約含1000個(gè)腸溶衣微丸。不可以咀嚼和碾碎服用，可溶于水或微酸性水（果汁）中，30分鐘內(nèi)服用。（Therapeutic注射口服制黏膜用制呼吸道給藥制靶向給藥系急癥：舌下含服、靜脈注 局部粘膜：滴眼劑、滴耳療效提副作用使用方攜帶方方 象的生物因素與藥效三者之間的關(guān)系三、TheclinicalapplicationoftheoraldosageAbsorptionoforalFirstpassFirstpasseffect首過(guò)效Afteradrugisswallowed,itisabsorbedbythedigestivesystemandentersthehepaticportalsystem.Itiscarriedthroughtheportalveinintotheliverbeforeitreachesthesystemiccirculation.Theliverorgutmetabolizemanydrugs,sometimestosuchanextentthatonlyasmallamountofactivedrugemergesfromtheliverorguttotherestofthecirculatorysystem.Thisfirstpassthroughtheliverthusgreatlyreducesthebioavailabilityofthedrug.DrugDrugdisintegration藥物 藥物（Drug）與輔料（excipients） Tablets-體積小，攜帶 方便 Tablets-attentions片劑問(wèn) 出度（dissolutionrate）和生物利用度（Bioavailability） ClassificationofTablets普通片劑（uncoatedtablets）：藥物與輔料均勻混合后，經(jīng)壓片機(jī) 包衣片（coatedtablets）：在片芯外包上衣膜，達(dá)到保護(hù)、美觀、改變口泡騰片（Effervescenttablets） 片中加入崩解劑，遇水后產(chǎn)生 口含片（BuccalTablets）：藥物含于口腔，使藥物在口腔或咽喉產(chǎn)生持久 舌下片（SublingualTablets）：藥物置于舌下迅速溶化，經(jīng)舌下靜脈直接 分散片（DispersibleTablets）：在水中迅速崩解均勻分散的片劑。主要為片劑的片劑的分類（ClassificationofHowtoHowtouseaspirineffervescent怎樣服用泡騰片Thefunctionof Lozengehan 腸溶片：整個(gè)吞服，用一杯水送下，不可隨意掰開(kāi)服或咀嚼、碾碎服用 分散片：可加水分散后飲用、口含、咀嚼或整個(gè)吞服 口含片；將藥物在口腔慢慢溶化，不宜整片咽 2、Capsules膠囊硬膠囊（hard軟膠囊（soft腸溶膠囊（enteric-coated緩釋膠囊（sustained-release2、Capsules膠囊hard藥物或藥物加輔料制成勻粉末或顆粒softcapsules：將一定量藥液或藥物粉末等密封于球形或圓形的軟質(zhì)囊材enteric-coatedcapsules腸溶：將硬膠囊或軟膠囊經(jīng)藥用高子材料處理或用其他適宜方法加工而成，囊殼不溶于胃液，但能在腸液中崩解而釋放活性成分緩控在膠囊

釋藥速度的包衣顆?；蛭⑼栊苋パ跄懸戎?/p>

達(dá)吉膠囊（復(fù)方消化酶膠囊劑本藥采用分段崩解技術(shù)使三色藥片在胃上部、胃下部、十二指腸及小腸崩解，使酶的活性各自適宜的pH下發(fā)膠囊劑CharacteristicsCharacteristicsof藥物的穩(wěn)定性提高膠囊殼可保護(hù)藥物免受濕氣和空氣中可延緩或定時(shí)釋放藥物，將不同釋放速度的藥物顆粒按所 3、口服溶液（solutionsfor口服口服溶液（solutionsfor 四、Therationalapplicationof注射劑合理應(yīng)WHO公 處方 HistoryofHistoryofthedevelopmentofinfusion 靜脈靜脈輸液方式經(jīng)歷了第一代全開(kāi)放、第二代半開(kāi)放和第三代全封閉式三種1、Thedefinitionof注射劑定 Aninjectionisaninfusionmethodofputtingfluidintothebody,usuallywithasyringeandahollowneedlewhichispiercedthroughtheskintoasufficientdepthforthematerialtobeadministeredintothebody.粉粉藥水溶藥乳乳劑型注水不溶性水溶

不穩(wěn)穩(wěn)

混懸型注水不混懸型注2、2、注射劑分類(Clssificationof3.Administration3.Administrationroutefor注射劑給藥途油溶液和混懸液一般不能靜脈注 4.(Injectionlocationandabsorptionroute IntravenousIntramuscularSubcutaneous

PharmacokineticcharacteristicsPharmacokineticcharacteristicsofdosage劑型的藥動(dòng)學(xué)特點(diǎn)（drug-timecurve藥時(shí)曲線注射液用的溶劑（Solventsfor時(shí)亮菌甲素注射液事“丙二醇”－ “丙二醇”:藥用溶劑，供肌肉、靜脈等給藥 ”:工業(yè)用溶劑，在 1937年磺胺酏劑造成358人,107人死亡的事件,就是增溶劑代替而產(chǎn)生毒5.Characteristicsof注射劑特注射劑優(yōu)勢(shì)藥效迅速、可靠，不受消化液和食物的影適于不能口服的藥物（青霉素、胰島素適于不能口服的給藥可以產(chǎn)生局部定位作用 、造影劑Characteristicsof注射劑特使用不便不 安全性侵入式給藥，疼痛、避開(kāi) Thequalitydemandsof注射劑質(zhì)量無(wú)菌Sterile澄明度Clarity:注射劑在規(guī)定條件下檢查，不得有肉眼可滲透壓Osmoticpressure:盡可能與血液相等穩(wěn)定性Stability:物理、化學(xué)和生物穩(wěn)定性（2年以上Pyrogen 、虛脫甚至出現(xiàn)生。欣弗事 量，滅菌過(guò)程的熱分布不均勻。注射劑澄明度注射劑澄明度可見(jiàn)異物（visible不溶性微粒（Insolublevisiblevisiblematter注射液可見(jiàn)異物檢注射劑可見(jiàn)微粒檢查條件（燈檢法（檢查有色異物 注射液可見(jiàn)異物檢 燈檢法:除去容器，擦凈容器外壁，輕輕旋轉(zhuǎn)和翻Insoluble 塑料、橡膠、玻璃屑、中藥膠體微粒等。 終端過(guò)濾終端過(guò)濾器安全有效的控制微粒方法：終端過(guò)濾器可預(yù)防的藥品不良事 RubberRubberplugF級(jí)案例：血凝酶與凝血醫(yī)師醫(yī) 藥師發(fā)靜注靜注、肌注或皮下注射，也可局部用嚴(yán)禁注F級(jí) PHPHand靜脈PH值為6.320%的靜脈發(fā)生輕度靜脈炎PH值為6.5，沒(méi)有靜脈炎發(fā)FrankGe,崔晶晶輸液導(dǎo)致靜脈炎的因素分析[J]多巴阿昔多巴安達(dá)鹽酸胺碘

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大侖萬(wàn)古霉泮托拉唑01234567890123456789 生理 5%GS、10%、50%葡萄糖：PH=3.2-0.9%、10PH=4.5-5%葡萄糖氯化鈉：PH=3.5-復(fù)方氯化鈉：PH=4.5-乳酸鈉林格：PH=6.0-滅菌注射用水：PH=5-5%碳酸氫鈉：PH=7.5-低分子右旋糖苷葡萄糖：PH=3.5-20%甘露醇：PH=4.5-甘油果糖：PH=3.0-TheeffectofpHonstabilityofdrugTheeffectofpHonstabilityofdrugPH

交叉過(guò)敏決定TheeffectofTheeffectofpHonstabilityofdrugPH

C-CH- +RCONHCH2-RCONHCH2-青霉阿昔洛 阿昔洛韋頭孢米諾鈉頭孢米頭孢米諾鈉

TheTheeffectofcompatibilitiesofdrugson配伍對(duì)注射劑穩(wěn)定性的影 TheTheeffectofcompatibilitiesofdrugson配伍對(duì)注射劑穩(wěn)定性的影 +VitcFeCL3Vitc氧化還原溶媒對(duì)溶媒對(duì)注射液穩(wěn)定性的影 5%葡萄糖 生理鹽

持續(xù)泵入6持續(xù)泵入6大約8個(gè)小時(shí)泵僅使用等滲的葡萄糖溶液中國(guó)藥師，2006，9（12）:1130-滲透壓 純?nèi)軇┫蛉芤簼B透的壓滲透壓的形滲透半透純?nèi)芗內(nèi)搜獫{滲透如：0.45%

滲透壓的性溶質(zhì)顆粒數(shù)目的多少（質(zhì)濃度）成正比，注射液滲透壓計(jì)算已知溶液的百分濃度X溶質(zhì)溶質(zhì)分子

1000ML中所含溶質(zhì)的×1000f溶質(zhì)顆粒數(shù)注射液滲透壓計(jì)算等滲氯化鈉注射液1000ml化鈉？血漿平均滲透壓為298mOsmol。解：∵1mmol/L的氯