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TheprofessionalEnglishofpharmaceuticalengineeringWangHaifengPART3INDUSTRIALPHARMACYUnit13SterileProducts无菌产品无菌产品是不含活体微生物的治疗剂剂型，其主要包括非肠道用的、眼用的和冲洗用的制剂。这之中，非肠道用产品在药物剂型当中是（较为）特别的因为它们是通过皮肤和黏膜被注射到人体内部的。SterileProductsSterileProductsaredosageformsoftherapeuticagentsthatarefreeofviablemicroorganisms.Principally,theseincludeparenteral,ophthalmic,andirrigatingpreparations.Ofthese,parenteralproductsareuniqueamongdosageformsofdrugsbecausetheyareinjectedthroughtheskinormucousmembranesintointernalbodycompartment.这样，由于它们进入了高效率的人体第一道免疫防线——皮肤和黏膜，（所以）它们必须没有微生物感染和有毒成分，同时又（必须）具有特别高的纯度。这些产品的制备过程中涉及到的所有组分和（工艺）流程都必须经过选择和设计以尽可能地消除各种类型的污染，无论是来自物理的、化学的，还是微生物的。Thus,becausetheyhavecircumventedthehighlyefficientfirstlineofbodydefense,theskinandmucousmembranes,theymustbefreefrommicrobialcontaminationandfromtoxiccomponentsaswellaspossessanexceptionallyhighlevelofpurity.Allcomponentsandprocessesinvolvedinthepreparationoftheseproductsmustbeselectedanddesignedtoeliminate,asmuchaspossible,contaminationofalltypes,whetherofphysical,chemical,ormicrobiologicorigin.Preparationsfortheeye,thoughnotintroducedintointernalbodycavities,areplacedincontactwithtissuesthataresensitivetocontamination.Therefore,similarstandardsarerequiredforophthalmicpreparations.眼用制剂尽管没有被引入到内部体腔，但它仍与对污染（物）敏感的组织有接触，因此，对眼用制剂也要求（与非肠道用制剂）类似的标准。Irrigatingsolutionsarenowalsorequiredtomeetthesamestandardsasparenteralsolutionsbecauseduringanirrigationprocedure,substantialamountsofthesesolutionscanenterthebloodstreamdirectlythroughopenbloodvesselsofwoundsorabradedmucousmembranes.Therefore,thecharacteristicsandstandardspresentedinthischapterfortheproductionoflarge-volumeparenteralsolutionsapplyequallytoirrigatingsolutions.冲洗液现在也要求满足和非肠道用溶液一样的标准，因为在冲洗过程中，大量的冲洗液都可以通过伤口的敞开血管或者擦伤的黏膜组织直接进入到血流中/血液。因此，本章中描述的有关非肠道用大容量输液生产的特点和标准，对于冲洗液同样适用。Sterileproductsaremostfrequentlysolutionsorsuspensions,butmayevenbesolidpelletsfortissueimplantation.Thecontrolofaprocesstominimizecontaminationforasmallquantityofsuchaproductcanbeachievedwithrelativeease.Asthequantityofproductincrease,theproblemsofcontrollingtheprocesstopreventcontaminationmultiply.Therefore,thepreparationofsterileproductshasbecomeahighlyspecializedareainpharmaceuticalprocessing.Thestandardsestablished,theattitude,theattitudeofpersonnel,andtheprocesscontrolmustbeofasuperiorlevel.无菌产品通常是溶液或者悬浮液，但甚至也可以是用于组织植入的固体药丸。对于少量的这种产品，使其污染降到最低的工艺控制可以相对容易地实现。（但）随着产品量的增加，控制工艺流程从而防止污染的困难也会增加。因而，无菌产品的制备已经成为药品生产里一个高度专业化领域。标准的制定、人员的态度和工艺流程的控制都必须有着优秀的水平。VehiclesByfarthemostfrequentlyemployedvehicleforsterileproductsiswater,sinceitisthevehicleforallforallnaturalbodyfluids.ThesuperiorqualityrequiredforsuchuseisdescribedinthemonographonWaterforInjectionintheUSP.Requirementsmaybeevenmorestringentforsomeproducts,however.溶媒/溶剂到目前为止，最常被用于无菌产品的溶媒就是水，因为水（也）是所有自然体液的溶媒。该用途所要求的优良特性在《美国药典》的《注射用水》专题论文中有所描述。但对于某些产品来说，要求可能会更为苛刻。Oneofthemostinclusivetestsforthequalityofwateristhetotalsolidscontent,agravimetricevaluationofthedissociatedandundissociatedorganicandinorganicsubstancespresentinthewater.However,alesstime-consumingtest,theelectrolyticmeasurementofconductivityofthewater,istheonemostfrequentlyused.Instantaneousmeasurementscanbeobtainedbyimmersingelectrodesinthewaterandmeasuringthespecificconductance,ameasurementthatdependsontheioniccontentofthewater.水质检验的一种最普遍的测试就是固形物总含量，一种对水中解离的和不解离的有机物和无机物在重量上的评估。然而，一种用时较少的测试——水导电性的电解测量——则是最常用的（测试方法），它通过把电极浸入水中测出具体的电导率，就可以实现即刻测量，是一种基于水中离子含量的测量方法。Theconductancenaybeexpressedbythemeterscaleasconductivityinmicromhos,resistanceinmegohms,orioniccontentaspartspermillion(ppm)ofsodiumchloride.Thevalidityofthismeasurementasanindicationofthepurityofthewaterisinferentialinthatmethodsofproducinghigh-puritywater,suchasdistillationandreverseosmosis,canbeexpectedtoremoveundissociatedsubstancesalongwiththosethataredissociated.电导率可以通过表头刻度盘以电导／微姆欧、电阻／兆欧姆或者离子含量／百万分之一NaCl的形式显示出来。作为水纯度的指示，这种测量方法的正确性只是推理性的，因为一些生产高纯度水的方法，比如蒸馏和反渗透，可以将不解离的物质同那些解离的物质一起除去。Undissociatedsubstancessuchaspyrogens,however,couldbepresentintheabsenceofionsandnotbedisclosedbythetest.Therefore,forcontaminantsotherthanions,additionaltestsshouldbeperformed.但是不解离的物质例如热原，可以以非离子的形式存在，因而不能被这种方法检测出来。因此，对于除离子之外的（其他）污染物，还需要进行另外的检测。AdditionaltestsforqualityofWaterforInjectionwithpermittedlimitsaredescribedintheUSPmonographs.WhencomparingthetotalsolidspermittedforWaterInjectionwiththatforSterileWaterforInjection,onewillnotethatconsiderablyhighervaluesarepermittedforSterileWaterforInjection.Thisisnecessarybecausethelatterproducthasbeensterilized,usuallybyathermalmethod,inacontainerthathasdissolvedtosomeextentinthewater.美国药典中有专著描述特殊用途的注射用水的水质附加测试。当把注射用水和无菌注射用水所允许的总固体量做比较时，你会发现无菌注射用水允许有相当高的(总固体量)值。这是必要的，因为后者是经过灭菌的，通常是通过一种热途径，容器在一定程度上溶解于水中。Therefore,thesolidscontentwillbegreaterthanforthenonsterilizedproduct.Ontheotherhand,the10ppmtotalsolidsofficiallypermittedforWaterforInjectionmaybemuchtoohighwhenusedasthevehicleformanyproducts.Inpractice,WaterforInjectionnormallyshouldnothaveaconductivityofmorethan1micromho(1megohm,approximately0.1ppmNaCl).因而，其固体含量会比没有灭菌的产品要高得多。另一方面，官方对于注射用水所允许的10ppm总固体量，对于许多产品的溶媒