制药工程专业英语 Unit 13 课文翻译_制药工程专业英语课文

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Unit 13Sterile Products

Sterile Products

Sterile products are dosage forms of therapeutic agents that are free of viable microorganisms.Principally，these include parenteral，ophthalmic，irrigating preparations.Of these, and parenteral products are unique among dosage forms of drugs because they are injected through the skin or mucous membranes into internal body compartment.Thus，because they have circumvented the highly efficient first line of body defense，the skin and mucous membranes，they must be free from microbial contamination and from toxic components as well as poe an exceptionally high level of purity.All components and procees involved in the preparation of these products must be selected and designed to eliminate，as much as poible，contamination of all types，whether of physical，chemical，or microbiologic origin.Preparations for the eye, though not introduced into internal body cavities，are placed in contact with tiues that are very sensitive to contamination.Therefore，similar standards are required for ophthalmic preparations).Irrigating solutions are now also required to meet the same standards as parenteral solutions because during an irrigation procedure，substantial amounts of these solutions can enter the bloodstream directly through open blood veels of wounds or abraded mucous membranes.Therefore，the characteristics and standards presented in this chapter for the production of large-volume parenteral solutions apply equally to irrigating solutions.Sterile products are most frequently solutions or suspensions，but may even be solid pellets for tiue implantation.The control of a proce to minimize contamination for a small quantity of such a product can be achieved with relative ease.As the quantity of product increases，the problems of controlling the proce to prevent contamination multiply.Therefore，the preparation of sterile products has become a highly specialized area in pharmaceutical proceing.The standards established，the attitude of personnel，and the proce control must be of a第13 单元 无菌产品 无菌产品 无菌产品是不含微生物活体的治疗剂剂型，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。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。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。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敞开的血管伤口或者擦伤的黏膜组织直接进入到血液。因此，本章中描述的有关非肠道用溶液大批量生产的特点和标准，对于冲洗液同样适用。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对端植入的固体药丸。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加工里一个高度专业化的领域。制定的标准、人员的态度和工艺流程的控制都必须有着优秀的水平。

superior level.Vehicles

By far the most frequently employed vehicle for sterile

products is water，since it is the vehicle for all natural body

fluids.The superior quality required for such use is

described in the monograph on Water for Injection in the

USP.Requirements may be even more stringent for some

products，however.One of the most inclusive tests for the quality of water is

the total solids content，a gravimetric evaluation of the

diociated and undiociated organic and inorganic

substances present in the water.However，a le

time-consuming test，the electrolytic measurement of

conductivity of the water，is the one most frequently used.Instantaneous measurements can be obtained by immersing

electrodes in the water and measuring the specific

conductance, a measurement that depends on the ionic

content of the water.The conductance may be expreed by

the meter scale as conductivity in micromhos，resistance in

megohms , or ionic content as parts per million(ppm)of

sodium chloride.The validity of this measurement as an

indication of the purity of the water is inferential in that

methods of producing high-purity water，such as distillation

and reverse osmosis，can be expected to remove

undiociated substances along with those that are

diociated.Undiociated substances such as pyrogens，however，could be present in the absence of ions and not be

disclosed by the test.Therefore，for contaminants other than

ions，additional tests should be performed.Additional tests for quality of Water for Injection with

permitted limits are described in the USP monographs.When comparing the total solids permitted for Water for

Injection with that for Sterile Water for Injection，one will

note that considerably higher values are permitted for Sterile

Water for Injection.This is neceary because the latter

product has been sterilized，usually by a thermal method，in

a container that has diolved to some extent in the water.Therefore，the solids content will be greater than for the

nonsterilized product.On the other hand，the 10 ppm total

solids officially permitted for Water for Injection may be

much too high when used as the vehicle for many products.In practice, Water for Injection normally should not have a

conductivity of more than 1 micromho(1 megohm，approximately 0.1 ppm NaCl).溶媒 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。水质检验的一种最普遍的测试就是固体总含量，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。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／ppm 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。但是不解离的物质例如热原，可以不以离子的形式存在，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。具有特殊用途的注射用水的水质附加测试在美国药典中有专篇描述。当把注射用水和无菌注射用水所允许的固体总含量做比较时，你会发现无菌注射用水允许有相当高的值。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，在一个在一定程度上溶解于水的容器中。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10 ppm的固体总含量，对于许多产品来说，作为溶媒其值可能都太高了。事 实上，注射用水其电导一般不应 该超过1微姆欧（1兆欧，大约 0.1 ppm NaCl）。

Added Substances.添加剂

Substances added to a product to enhance its stability are 添加到产品当中用以提高产品稳eential for almost every product.Such substances include 定性的物质，对于几乎每种产品solubilizers，antioxidants，chelating agents，buffers，来说都是必不可少的。这样的物tonicity contributors，antibacterial agents，antifungal 质包括增溶剂、抗氧剂、螯合剂、agents，hydrolysis inhibitors，antifoaming agents，and 缓冲剂、tonicity contributor、抗numerous other substances for specialized purposes.At the 菌剂、杀菌剂、水解抑制剂、消same time，these agents must be prevented from adversely 沫剂和许多其他的有专门用途的affecting the product.In general，added substances must be 物质。同时，这些组分必须不能nontoxic in the quantity administered to the patient.They 对产品有不利影响。一般来说，should not interfere with the therapeutic efficacy nor with 添加剂必须在病人的给药量范围the aay of the active therapeutic compound.They must 内是无毒的。它们不应该干扰（产also be present and active when needed throughout the 品的）治疗效果，也不能干扰有useful life of the product.Therefore，these agents must be 效活性化合物的测定。在产品的selected with great care，and they must be evaluated as to 整个有效期内，需要它们时，它their effect upon the entire formulation.-An extensive 们必须存在并且有效。因此，对review of excipients used in parenteral products and the 这些物质必须非常小心地进行挑means for adjusting pH of these products has recently been 选，而且对它们对整个配方的影published and should be referred to for more detailed 响也必须进行评估。一篇关于用information.在非肠道用产品中的赋形剂和调节这些产品pH的方法的综述，最近已经出版，更多的详细信息 可参阅之。

Formulation配方

The formulation of a parenteral product involves the 非肠道用产品的配方涉及一个或combination of one or more ingredients with a medicinal 者更多组成部分间的结合，这些agent to enhance the convenience，acceptability，or 组成部分（各自）都含有一种用effectivene of the product.Rarely is it preferable to 以提高产品方便性、可接受性或dispense a drug singly as a sterile dry powder unle the 者疗效的有效成分。（人们）很少formulation of a stable liquid preparation is not poible.愿意把药物仅仅以一种无菌的、On the other hand，a therapeutic agent is a chemical 干燥的粉末（的形式）配售，除compound subject to the physical and chemical reactions 非（把它做成）稳定的液体制剂characteristic of the cla of compounds to which it belongs.的配方是行不通的。Therefore，a careful evaluation must be made of every 另一方面，治疗剂（药物的有效combination of two or more ingredients to ascertain whether or not adverse interactions occur，and if they do，of ways to 的物理和化学反应特性的一种化modify the formulation so that the reactions are eliminated 合物。因此对每一个两种或更多or minimized.The formulation of sterile products is 组成部分间的结合都必须有一个challenging，therefore，to the knowledge and ingenuity of 仔细的评估，弄清楚会不会有不the persons responsible.The amount of information 良反应发生。如果有，则须找到

available to the formulator concerning the physical and 改进配方的方法以使反应消除或chemical properties of a therapeutic agent，particularly if it is 者降低到最小。因此，无菌产品a new compound，is often quite meager.Information 的配方是对负责人员知识和独创concerning basic properties muse be obtained，including 性的一个挑战。配方设计师可得molecular weight，solubility，purity，colligative properties，到的关于治疗剂（药物的有效成and chemical reactivity，before an intelligent approach to 分）物理和化学性质的信息量通formulation can begin.Improvements in formulation are a 常是很少的，尤其当治疗剂是一continuing‘ proce，since important properties of a drug or 种新的化合物时。关于（治疗剂）of the total formulation may not become evident until the 基本性质的信息，包括分子量、product has been stored or used for a prolonged time: 溶解度、纯度、依数性和化学反However，because of the extensive test documentation 应性，必须在一种好的组建配方required by the U.S.Food and Drug Administration(FDA)，的方法可以开始之前得到。配方only outstanding formulations can be justified for 的改善是一个连续不断的过程，continuance to the state of a maketed product.因为药物或整体配方的一些重要 性质只有在贮存或者使用了很长 时间之后才可能会变得明显。然 而，由于美国食品及药物管理局 大量的测试要求文件，（使得）只 有那些杰出的配方才能继续发展 成为上市产品。

生产

Production 生产过程包括从配方的各个组成 The production proce includes all of the steps from the 部分的积聚和结合到产品封装入accumulation and combining of the ingredients of the 用于分售的单个包装内的所有步formula to the enclosing of the product in the individual 骤。和这些过程有紧密联系的是container for distribution.Intimately aociated with these 搬运人员和执行这些步骤的设procees are the personnel who carry them out and the 备。计划出来的最理想的过程也facilities in which they are performed.The most ideally 会因为没有正确态度或没有接受planned procees can be rendered ineffective by personnel 正确培训的人员或者不能提供一who do not have the right attitude or training，or by facilities 个有效的控制环境的设备而变得that do not provide an efficiently controlled environment.无效。

To enhance the aurance of succeful manufacturing 为了增加成功的生产操作的保operation，all proce steps must be carefully reduced to 证，所有的过程步骤在证明是有writing after being shown to be effective.These written 效的之后都要仔细地归纳成书面proce steps are often called standard.operating procedures 材料，这些书面的过程步骤经常(SOPs)⑥.No extemporaneous changes are permitted to be 被称为标准操作规程（SOPs）。made in these procedures;any change must go through the 这些规程是不允许进行临时改动same approval steps as the original written SOP.Further，的;任何改动都必须经过和原有extensive records must be kept to give aurance at the end 的书面规程一样的证明步骤的证of the production proce that all steps have been performed 明。而且，还需要做大量的记录，as prescribed，an aspect emphasized in the FDA's Good 以便在生产过程的最后用来保Manufacturing Practices.Such in-proce control is eential 证：所有的步骤都是按照规定执to auring the quality of the product，since these aurances 行的。这是美国食品及药物管理are even more significant than those from product release 局药品生产质量管理规范中所强

testing.The production of.a quality product is a result of the 调的一个方面。这些中间控制对continuous，dedicated effort of the quality aurance，于保证产品的质量来说是必要

production，and quality control personnel within the plant in 的，因为这些保证甚至比产品发developing，performing，and confirming effective sops.行测试的控制还重要。一件优质Selected from Lachman Leon et al.The Theory and Practice 产品的生产，是车间里在开发、of Industrial Pharmacy, 3rd ed.，Lea and Febiger, 执行和确认有效标准操作规程中Philadelphia，1986.的那些品质保证、生产和质量控 制人员不懈而专注的努力的结 果。