常用药物剂型与临床应用

常用药物剂型与临床应DosageFormandClinicalDepartmentofXuanwuHospitalofCapitalMedicalUniversityYanSuying学习目LearningAfterlearningthisclass,thestudentwillbeableTheclinicalapplicationoforal,sustained-release,andinjection口服剂型、缓控释剂型、注射剂临床应用特Explainthedifferencebetweendosageformandrouteof剂型与给药途径的区ClassificationandcharacteristicsofdosageThequalityoftheinjections注射剂质量要Compareandcontrasttheadvantages/disadvantagesofvariousdrugdosageforms比较各种剂型的优势与劣势DesignofdrugformsDosage 胶囊剂 片剂

注射剂HaveyoueverseenHaveyoueverseentheDosage

吸入剂

贴剂 6WhatisdrugdosageTheclassificationofdrugdosageformsand ClinicalapplicationoforaldosageformsHowtorationallyuseInjection（注射剂合理应用NewDrugdeliverysystem（新型给药系统7(ConceptsofdosageDosageformisthephysicalformof(ConceptsofdosageThereareabout40variatiesofcommondosageforms.8一、药物剂型分类与特(classificationandcharacteristicsofdosage9classificationclassificationofdosageDependingonthemethod/routeofadministration,dosageformscomeinseveraltypes.Theseincludemanykindsofliquid,solid,andsemisoliddosageCommondosageformsincludepill,tablet,orcapsule,drinkorsyrup,andnaturalorherbalformsuchasplantorfoodofsorts,amongmanyNotably,therouteofadministration(ROA)fordrugdeliveryisdependentonthedosageformofthesubstanceinquestion.（一）Classificationbyroutesofadministration:six(按给药途径分六类Oraldosageforms:tablet,capsule,Powder,Solution,syrup Parenteraldosageforms:Solutionorsuspensionfor胃肠外给药 Rectaldosageforms：enema,直肠给药 灌肠剂、栓剂等Inhaleddosageforms:aerosol,Inhaler&MetereddoseTopicaldosageforms：cream(oil/water≈1)，ointment(oilMucosaldosageforms：eyedrops(ophthalmic),eardrops,skin ClassificationsClassificationsbypatternsThisclassificationmethodismoreusefulinThisclassificationmethodismoreusefulinthepreparation,storageandtransportationof液体剂型：Soliddosageform:granules,tablets,capsulesSemisoliddosageform:ointment,gelGasdosageform:aerosol,sprayet气体剂型：气雾剂、喷雾剂等（三）新给药剂型New（三）新给药剂型NewDrugdeliveryMicro-capsule微囊 微 transdermalplastics透皮ingdrug-deliverysystem靶向给药系Delayed-release Oraldosage 44Mucosaldosageforms Injection注射 ApharmaceuticalApharmaceuticaldrugcanbemadeintoavarietyofApharmaceuticaldrugcanbemadeintoavarietyofVariousdosageformsmayexistforthesamedifferentmedicalconditionsmaywarrantdifferentroutesofForexample,persistentvomiting（持续 ）maymakeitdifficulttouseanoraldosageform;inthiscase,itmaybeadvisabletouseeitheraninjectionorasuppository.Also,specificdosageformsmaybewarrantedforcertainmedications,sincetheremaybeproblemswithstability,e.g.insulincannotbegivenorallysinceitisdigestedbythegut.TheeffectofthedrugdosageTheeffectofthedrugdosageformsonthedrugFastacting：injections,sublingualtablet(glyceryl速效：注射剂、舌下含片（硝酸甘油Slowactingorlong-acting：sustained-releasepreparations慢效或长效制剂：缓控释制剂（硝苯地平Alteringthenatureofthedrugfunction25%magnesiumsulfateinjection（intravenousinfusion）—inhibit50%magnesiumsulfatesolutionoral—Reducingadversedrugeffectsindometacincapsulescauselargegastrointestinal吲哚美辛胶囊—indometacinsuppositoriesreducegastrointestinal吲哚美辛拴剂—TheeffectofthedrugdosageformsonthedrugPositioning ing定位和靶向作用amphotericinBliposome-mainlygatheronreticularepithelialcells，reducingkidney两性霉素B Alteringthestabilityofthedrugpenicillinpowder>>>penicillinInfluencingthedrugNifedipine–nifedipinesuspentionToimprovepatients’medicationsustained（controlled）releasetablet缓（控）释片transdermalplastics透皮贴药物剂型的重要Importanceofdosage1Increased2improvethe3ReducetheadversedrugTheThepharmacokineticcharacteristicsofdifferentdosageforms(drug-timecurve)二、药物剂型/制剂设DesignofDosageForm/PreparationandClinicalEfficacy（一）（一）DesignofDosageThefeatureofpharmacodynamicsandThephysicochemicalpropertyofThedemandofclinicalAbsorptionAbsorptioneffectsdependonthedrugdosageThefeatureofbiopharmaceutics—routesof生物药剂学特征—给药途生物利用RouteofAcetaminophen对乙酰氨基Oral（口服Aspirin阿司匹Oral（口服Oral口Injection肌Gentamycin庆大霉肌Gentamycin庆大霉口服(胃肠道疾病IfIfthebioavailabilityisabove0.6(60%),drugisdesignedasoral一般生物利用度在0.6（60%）以上，设计为口Ifthebioavailabilityisbelow0.3(30%),drugisdesignedasinjection生物利用度在0.3（30%）以下，设计为注射2.The2.ThephysicochemicalpropertiesofPhysicalappearance物理状态soliddrug固体：新药研发时，口服有效，设计考虑次序：胶囊—片剂Liquiddrug液体：softcapsuleLiposolubility脂溶性：易于透过细胞膜，口服制Thestabilityingastrointestine药物在胃肠道中的稳定性(digestiveenzyme消化酶gastricacid胃酸PenicillinInterferonInsulinOmeprazoleenteric-coatedUnstableinacidicenvironment.The20mgtabletdispersesrapidlyinthestomachtoreleaseabout1,000small(0.5mm)individuallyentericcoatedmicropellets.Itcannotbechewedorground.Itissolubleinwaterorweakacidicsolution(juice),takenwithin30mins.酸性环境不稳定，由肠溶衣微丸组成。每片20毫克口服片剂中大约含1000个肠溶衣微丸。不可以咀嚼和碾碎服用，可溶于水或微酸性水（果汁）中，30分钟内服用。（Therapeutic注射口服制黏膜用制呼吸道给药制靶向给药系急症：舌下含服、静脉注 局部粘膜：滴眼剂、滴耳疗效提副作用使用方携带方方 象的生物因素与药效三者之间的关系三、TheclinicalapplicationoftheoraldosageAbsorptionoforalFirstpassFirstpasseffect首过效Afteradrugisswallowed,itisabsorbedbythedigestivesystemandentersthehepaticportalsystem.Itiscarriedthroughtheportalveinintotheliverbeforeitreachesthesystemiccirculation.Theliverorgutmetabolizemanydrugs,sometimestosuchanextentthatonlyasmallamountofactivedrugemergesfromtheliverorguttotherestofthecirculatorysystem.Thisfirstpassthroughtheliverthusgreatlyreducesthebioavailabilityofthedrug.DrugDrugdisintegration药物 药物（Drug）与辅料（excipients） Tablets-体积小，携带 方便 Tablets-attentions片剂问 出度（dissolutionrate）和生物利用度（Bioavailability） ClassificationofTablets普通片剂（uncoatedtablets）：药物与辅料均匀混合后，经压片机 包衣片（coatedtablets）：在片芯外包上衣膜，达到保护、美观、改变口泡腾片（Effervescenttablets） 片中加入崩解剂，遇水后产生 口含片（BuccalTablets）：药物含于口腔，使药物在口腔或咽喉产生持久 舌下片（SublingualTablets）：药物置于舌下迅速溶化，经舌下静脉直接 分散片（DispersibleTablets）：在水中迅速崩解均匀分散的片剂。主要为片剂的片剂的分类（ClassificationofHowtoHowtouseaspirineffervescent怎样服用泡腾片Thefunctionof Lozengehan 肠溶片：整个吞服，用一杯水送下，不可随意掰开服或咀嚼、碾碎服用 分散片：可加水分散后饮用、口含、咀嚼或整个吞服 口含片；将药物在口腔慢慢溶化，不宜整片咽 2、Capsules胶囊硬胶囊（hard软胶囊（soft肠溶胶囊（enteric-coated缓释胶囊（sustained-release2、Capsules胶囊hard药物或药物加辅料制成匀粉末或颗粒softcapsules：将一定量药液或药物粉末等密封于球形或圆形的软质囊材enteric-coatedcapsules肠溶：将硬胶囊或软胶囊经药用高子材料处理或用其他适宜方法加工而成，囊壳不溶于胃液，但能在肠液中崩解而释放活性成分缓控在胶囊

释药速度的包衣颗粒或微丸熊去氧胆胰脂

达吉胶囊（复方消化酶胶囊剂本药采用分段崩解技术使三色药片在胃上部、胃下部、十二指肠及小肠崩解，使酶的活性各自适宜的pH下发胶囊剂CharacteristicsCharacteristicsof药物的稳定性提高胶囊壳可保护药物免受湿气和空气中可延缓或定时释放药物，将不同释放速度的药物颗粒按所 3、口服溶液（solutionsfor口服口服溶液（solutionsfor 四、Therationalapplicationof注射剂合理应WHO公 处方 HistoryofHistoryofthedevelopmentofinfusion 静脉静脉输液方式经历了第一代全开放、第二代半开放和第三代全封闭式三种1、Thedefinitionof注射剂定 Aninjectionisaninfusionmethodofputtingfluidintothebody,usuallywithasyringeandahollowneedlewhichispiercedthroughtheskintoasufficientdepthforthematerialtobeadministeredintothebody.粉粉药水溶药乳乳剂型注水不溶性水溶

不稳稳

混悬型注水不混悬型注2、2、注射剂分类(Clssificationof3.Administration3.Administrationroutefor注射剂给药途油溶液和混悬液一般不能静脉注 4.(Injectionlocationandabsorptionroute IntravenousIntramuscularSubcutaneous

PharmacokineticcharacteristicsPharmacokineticcharacteristicsofdosage剂型的药动学特点（drug-timecurve药时曲线注射液用的溶剂（Solventsfor时亮菌甲素注射液事“丙二醇”－ “丙二醇”:药用溶剂，供肌肉、静脉等给药 ”:工业用溶剂，在 1937年磺胺酏剂造成358人,107人死亡的事件,就是增溶剂代替而产生毒5.Characteristicsof注射剂特注射剂优势药效迅速、可靠，不受消化液和食物的影适于不能口服的药物（青霉素、胰岛素适于不能口服的给药可以产生局部定位作用 、造影剂Characteristicsof注射剂特使用不便不 安全性侵入式给药，疼痛、避开 Thequalitydemandsof注射剂质量无菌Sterile澄明度Clarity:注射剂在规定条件下检查，不得有肉眼可渗透压Osmoticpressure:尽可能与血液相等稳定性Stability:物理、化学和生物稳定性（2年以上Pyrogen 、虚脱甚至出现生。欣弗事 量，灭菌过程的热分布不均匀。注射剂澄明度注射剂澄明度可见异物（visible不溶性微粒（Insolublevisiblevisiblematter注射液可见异物检注射剂可见微粒检查条件（灯检法（检查有色异物 注射液可见异物检 灯检法:除去容器，擦净容器外壁，轻轻旋转和翻Insoluble 塑料、橡胶、玻璃屑、中药胶体微粒等。 终端过滤终端过滤器安全有效的控制微粒方法：终端过滤器可预防的药品不良事 RubberRubberplugF级案例：血凝酶与凝血医师医 药师发静注静注、肌注或皮下注射，也可局部用严禁注F级 PHPHand静脉PH值为6.320%的静脉发生轻度静脉炎PH值为6.5，没有静脉炎发FrankGe,崔晶晶输液导致静脉炎的因素分析[J]多巴阿昔多巴安达盐酸胺碘

利复

氟尿嘧

大仑万古霉泮托拉唑01234567890123456789 生理 5%GS、10%、50%葡萄糖：PH=3.2-0.9%、10PH=4.5-5%葡萄糖氯化钠：PH=3.5-复方氯化钠：PH=4.5-乳酸钠林格：PH=6.0-灭菌注射用水：PH=5-5%碳酸氢钠：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

交叉过敏决定TheeffectofTheeffectofpHonstabilityofdrugPH

C-CH- +RCONHCH2-RCONHCH2-青霉阿昔洛 阿昔洛韦头孢米诺钠头孢米头孢米诺钠

TheTheeffectofcompatibilitiesofdrugson配伍对注射剂稳定性的影 TheTheeffectofcompatibilitiesofdrugson配伍对注射剂稳定性的影 +VitcFeCL3Vitc氧化还原溶媒对溶媒对注射液稳定性的影 5%葡萄糖 生理盐

持续泵入6持续泵入6大约8个小时泵仅使用等渗的葡萄糖溶液中国药师，2006，9（12）:1130-渗透压 纯溶剂向溶液渗透的压渗透压的形渗透半透纯溶纯人血浆渗透如：0.45%

渗透压的性溶质颗粒数目的多少（质浓度）成正比，注射液渗透压计算已知溶液的百分浓度X溶质溶质分子

1000ML中所含溶质的×1000f溶质颗粒数注射液渗透压计算等渗氯化钠注射液1000ml化钠？血浆平均渗透压为298mOsmol。解：∵1mmol/L的氯