【正文】 icromho(1 megohm，approximately ppm NaCl).溶媒 到目前為止，最常被用于無菌產(chǎn)品的溶媒就是水，因為水（也）是所有自然體液的溶媒。該用途所要求的優(yōu)良特性在《美國藥典》的《注射用水》專題論文中有所描述。但對于某些產(chǎn)品來說，要求可能會更為苛刻。水質(zhì)檢驗的一種最普遍的測試就是固體總含量，一種對水中解離的和不解離的有機物和無機物在重量上的評估。然而，一種用時較少的測試——水導電性的電解測量——則是最常用的（測試方法），它通過把電極浸入水中測出具體的電導率，就可以實現(xiàn)即刻測量，是一種基于水中離子含量的測量方法。電導率可以通過表頭刻度盤以電導／微姆歐、電阻／兆歐姆或者離子含量／ppm NaCl的形式顯示出來。作為水純度的指示，這種測量方法的正確性只是推理性的，因為一些生產(chǎn)高純度水的方法，比如蒸餾和反滲透，可以將不解離的物質(zhì)同那些解離的物質(zhì)一起除去。但是不解離的物質(zhì)例如熱原，可以不以離子的形式存在，因而不能被這種方法檢測出來。因此，對于除離子之外的（其他）污染物，還需要進行另外的檢測。具有特殊用途的注射用水的水質(zhì)附加測試在美國藥典中有專篇描述。當把注射用水和無菌注射用水所允許的固體總含量做比較時，你會發(fā)現(xiàn)無菌注射用水允許有相當高的值。這是必要的，因為后者是經(jīng)過滅菌的，通常是通過一種熱途徑，在一個在一定程度上溶解于水的容器中。因而，其固體含量會比沒有滅菌的產(chǎn)品要高得多。另一方面，官方對于注射用水所允許的10 ppm的固體總含量，對于許多產(chǎn)品來說，作為溶媒其值可能都太高了。事 實上，注射用水其電導一般不應 該超過1微姆歐（1兆歐，大約 ppm NaCl）。Added Substances added to a product to enhance its stability are 添加到產(chǎn)品當中用以提高產(chǎn)品穩(wěn)essential for almost every substances include 定性的物質(zhì)，對于幾乎每種產(chǎn)品solubilizers，antioxidants，chelating agents，buffers，來說都是必不可少的。這樣的物tonicity contributors，antibacterial agents，antifungal 質(zhì)包括增溶劑、抗氧劑、螯合劑、agents，hydrolysis inhibitors，antifoaming agents，and 緩沖劑、tonicity contributor、抗numerous other substances for specialized the 菌劑、殺菌劑、水解抑制劑、消same time，these agents must be prevented from adversely 沫劑和許多其他的有專門用途的affecting the general，added substances must be 物質(zhì)。同時，這些組分必須不能nontoxic in the quantity administered to the 對產(chǎn)品有不利影響。一般來說，should not interfere with the therapeutic efficacy nor with 添加劑必須在病人的給藥量范圍the assay of the active therapeutic must 內(nèi)是無毒的。它們不應該干擾（產(chǎn)also be present and active when needed throughout the 品的）治療效果，也不能干擾有useful life of the ，these agents must be 效活性化合物的測定。在產(chǎn)品的selected with great care，and they must be evaluated as to 整個有效期內(nèi)，需要它們時，它their effect upon the entire extensive 們必須存在并且有效。因此，對review of excipients used in parenteral products and the 這些物質(zhì)必須非常小心地進行挑means for adjusting pH of these products has recently been 選，而且對它們對整個配方的影published and should be referred to for more detailed 響也必須進行評估。，最近已經(jīng)出版，更多的詳細信息 可參閱之。Formulation配方The formulation of a parenteral product involves the 非腸道用產(chǎn)品的配方涉及一個或bination of one or more ingredients with a medicinal 者更多組成部分間的結(jié)合，這些agent to enhance the convenience，acceptability，or 組成部分（各自）都含有一種用effectiveness of the is it preferable to 以提高產(chǎn)品方便性、可接受性或dispense a drug singly as a sterile dry powder unless the 者療效的有效成分。（人們）很少formulation of a stable liquid preparation is not 、On the other hand，a therapeutic agent is a chemical 干燥的粉末（的形式）配售，除pound subject to the physical and chemical reactions 非（把它做成）穩(wěn)定的液體制劑characteristic of the class of pounds to which it 。Therefore，a careful evaluation must be made of every 另一方面，治療劑（藥物的有效bination of two or more ingredients to ascertain whether or not adverse interactions occur，and if they do，of ways to 的物理和化學反應特性的一種化modify the formulation so that the reactions are eliminated 合物。因此對每一個兩種或更多or formulation of sterile products is 組成部分間的結(jié)合都必須有一個challenging，therefore，to the knowledge and ingenuity of 仔細的評估，弄清楚會不會有不the persons amount of information 良反應發(fā)生。如果有，則須找到available to the formulator concerning the physical and 改進配方的方法以使反應消除或chemical properties of a therapeutic agent，particularly if it is 者降低到最小。因此，無菌產(chǎn)品a new pound，is often quite 的配方是對負責人員知識和獨創(chuàng)concerning basic properties muse be obtained，including 性的一個挑戰(zhàn)。配方設計師可得molecular weight，solubility，purity，colligative properties，到的關(guān)于治療劑（藥物的有效成and chemical reactivity，before an intelligent approach to 分）物理和化學性質(zhì)的信息量通formulation can in formulation are a 常是很少的，尤其當治療劑是一continuing‘ process，since important properties of a drug or 種新的化合物時。關(guān)于（治療劑）of the total formulation may not bee evident until the 基本性質(zhì)的信息，包括分子量、product has been stored or used for a prolonged time: 溶解度、純度、依數(shù)性和化學反However，because of the extensive test documentation 應性，必須在一種好的組建配方required by the and Drug Administration(FDA)，的方法可以開始之前得到。配方only outstanding formulations can be justified for 的改善是一個連續(xù)不斷的過程，continuance to the state of a maketed 性質(zhì)只有在貯存或者使用了很長 時間之后才可能會變得明顯。然 而，由于美國食品及藥物管理局 大量的測試要求文件，（使得）只 有那些杰出的配方才能繼續(xù)發(fā)展 成為上市產(chǎn)品。生產(chǎn)Production 生產(chǎn)過程包括從配方的各個組成 The production process includes all of the steps from the 部分的積聚和結(jié)合到產(chǎn)品封裝入accumulation and bining of the ingredients of the 用于分售的單個包裝內(nèi)的所有步formula to the enclosing of the product in the individual 驟。和這些過程有緊密聯(lián)系的是container for associated with these 搬運人員和執(zhí)行這些步驟的設processes are the personnel who carry them out and the 備。計劃出來的最理想的過程也facilities in which they are most ideally 會因為沒有正確態(tài)度或沒有接受planned processes can be rendered ineffective by personnel 正確培訓的人員或者不能提供一who do not have the right attitude or training，or by facilities 個有效的控制環(huán)境的設備而變得that do not provide an efficiently controlled 。To enhance the assurance of successful manufacturing 為了增加成功的生產(chǎn)操作的保operation，all process steps must be carefully reduced to 證，所有的過程步驟在證明是有writing after being shown to be written 效的之后都要仔細地歸納成書面process steps are often called procedures 材料，這些書面的過程步驟經(jīng)常(SOPs)⑥.No extemporaneous changes are permitted to be 被稱為標準操作規(guī)程（SOPs）。made in these procedures。any change must go through the 這些規(guī)程是不允許進行臨時改動same approval steps as the original written ，的。任何改動都必須經(jīng)過和原有extensive records must be kept to give assurance at the end 的書面規(guī)程一樣的證明步驟的證of the production process that all steps have been performed 明。而且，還需要做大量的記錄，as prescribed，an aspect emphasized in the FDA39。s Good 以便在生產(chǎn)過程的最后用來保Manufacturing inprocess control is essential 證：所有的步驟都是按照規(guī)定執(zhí)to assuring the quality of the product，since these assurances 行的。這是美國食品及藥物管理are even more significant than those from product release 局藥品生產(chǎn)質(zhì)量管理規(guī)范中所強 production quality product is a result of the 調(diào)的一個方面。這些中間控制對continuous，dedicated effort of the quality assurance，于保證產(chǎn)品的質(zhì)量來說是必要production，and quality control personnel within the plant in 的，因為這些保證甚至比產(chǎn)品發(fā)developing，performing，and confirming effective 。一件優(yōu)質(zhì)Selected from Lachman Leon et Theory and Practice 產(chǎn)品的生產(chǎn)，是車間里在開發(fā)、of Industrial Pharmacy, 3rd ed.，Lea and Febiger, 執(zhí)行和確認有效標準操作規(guī)程中Philadelphia，、生產(chǎn)和質(zhì)量控 制人員不懈而專注的努力的結(jié) 果。