【独家】片剂和胶囊剂中用到的药用辅料
2016/3/23 药智网

    

    

     Overview of pharmaceutical excipients used in tablets and capsules片剂和胶囊剂中用到的药用辅料The pharmaceutical industry is ever thirsty to satisfy patient’s therapeutical needs and apart from active ingredients, inactive excipients play a major role in formulation development. Pharmaceutical excipients are substances other than the pharmacologically active drug or prodrug which are included in the manufacturing process or are contained in a finished pharmaceutical product dosage form.

     在制药行业为了满足患者的治疗需要而进行的药品配方的开发中,除了活性组分外,非活性的药用辅料也起重要作用。药用辅料虽然不像制药工艺中使用的药物或药物前体那样具有药理活性,但它也包含在已经完成的药品剂型中。In addition to transporting the active drug to the site in the body where the drug is intended to exert its action, excipients play an important part in the manufacturing process. They may also be important for keeping the drug from being released too early in the assimilation process in places where it could damage tender tissue and create gastric irritation or stomach upset.

     药用辅料除了把活性药物“运输”到人体的某个部位让药物在那里发挥作用外,在制药工艺中它还有一个重要的作用,就是避免药物在到达吸收部位之前过早释放从而损害脆弱的组织和产生胃刺激。

     Others help the drug to disintegrate into particles small enough to reach the blood stream more quickly and still others protect the product's stability so it will be at maximum effectiveness at time of use. In addition, some excipients are used to aid the identification of a drug product.

     有一些辅料可以帮助药物崩解成足够小的微粒,以便使其能够迅速达到血液中;还有一些辅料可以保持药品的稳定性,以便使其在使用时发挥最大效能。此外,某些辅料还可以用于辅助药品的识别。

     Last, but not least, some excipients are used simply to make the product taste and look better. This improves patient compliance, especially in children. Although technically "inactive" from a therapeutic sense, pharmaceutical excipients are critical and essential components of a modern drug product. In many products, excipients make up the bulk of the total dosage form (1). Apart from the drug’s active ingredient, other essential components include diluents or fillers, binders, disintegrants, lubricants, coloring agents and preservatives (3). Diluents or fillers are inert ingredients that can significantly affect the chemical and physical properties of the final tablet thus affecting the biopharmaceutical profile.

     最后,但并非最不重要的一点,某些辅料只是用来使药品的味道和外观更好些,尤其对于儿童来说,这可以改善患者依从性。尽管从治疗学的意义而言,药用辅料是“非活性的”,但在任何一种现代药品中,它们都是至关重要和必不可少的成分。在许多药品中,药用辅料构成了其总剂型的绝大部分(1)。除了药物活性组分外,其它重要组分,包括有稀释剂(或填充剂)、粘合剂、崩解剂、润滑剂、着色剂和防腐剂等(3)。稀释剂(或填充剂)虽然是惰性组分,它却能显著影响最终药品的化学和物理性质,从而影响其生物药学指标。

     One classic example of this are calcium salts, which can be utilized as fillers, which interfere with the absorption of tetracycline from the gastrointestinal tract. (4) This example emphasizes that excipients may not always be inert, as they may be perceived.此类情况的一个经典的例子是常用作填充剂的钙盐,它能干扰胃肠道对于四环素的吸收(4)。这个例子强调说明,药用辅料并不像人们认为的那样总是惰性的。

     Usually tablets are designed so that the smallest tablet size which can be conveniently compressed is formed. Thus, if the dose is small more diluents are required and if the dose is high less diluents are required as not to increase the tablet size, which might make it difficult to swallow.

     通常,片剂都设计成具有最小的体积,使其能够便于压缩成形。因此,如果剂量小,需用的稀释剂就多;剂量大,则需用的稀释剂就少,以便确保该片剂不因其增大体积而导致吞咽困难。

     Diluents selection should be made carefully as physical-chemical changes might render the product unstable and might cause problems in manufacturing. Binders are added to tablet formulations to add cohesiveness to powders thereby providing the necessary bonding to form granules which under compaction form a compact mass as tablet. In other words, binders are essential to achieve the “hardness” of the tablet.

     稀释剂的选择应慎重,因为一些物理-化学变化有可能导致药品的不稳定,还有可能在生产中引发一些问题。向片剂配方中加入粘合剂是为了使粉末增加粘性,在粉末的微粒之间提供必要的结合力使其形成颗粒,这些颗粒在压实过程中再进一步形成致密的片剂。换句话说,粘合剂对于片剂达到一定的“硬度”是必不可少的。

     Binders are usually selected on basis of previous experience, particular product needs, literature or vendor data or the preference of individual scientists or manufacturing unit. The primary criterion when choosing a binder is its compatibility with other tablet components.

     粘合剂的选择通常要依据既往的经验、药品的特定要求、参考文献或供应商提供的数据、工作人员个人或生产单位的偏好等。选择粘合剂的主要标准是它与片剂中其它组分的相容性。

     It must add sufficient cohesion to the powders to allow for normal processing yet allow the tablet to disintegrate and the drug to dissolve upon ingestion, releasing the active ingredients for absorption. Disintegrants facilitate the breakup of a tablet after oral administration.

     对于粉末不但要施加足够的结合力,使其能正常加工,还要使加工成的片剂在摄入后能够崩解,药物能够溶解,释放出活性组分而被吸收。崩解剂的作用是在片剂口服后促进其破碎。

     They can be added prior to granulation or during the lubrication step prior to compression or at both processing steps. The effectiveness of many disintegrants is affected by their position within the tablet. Since disintegration is the opposite operation to granulation (agglomeration) and the subsequent formation of strong compacts, one must carefully weigh these two phenomena when designing a tablet. Lubricants prevent sticking of the tablets to the tablet punches during the compression phase of the tablet manufacturing process.

     崩解剂可以在造粒前添加,或在压片前的润滑工序添加,或者在以上两个工序都添加。许多种崩解剂的效果受它们在片剂中的位置的影响。由于崩解是造粒(聚集)的逆过程以及随后形成的强压缩,在设计片剂加工工艺时必须认真权衡这两种现象。在片剂生产工艺中的压片工序,润滑剂用来防止片剂在压片机上发生粘附。

     When lubricants are added to a powder mass, they form a coat around individual particles which remains more or less intact during compression. Lubricants are mostly hydrophobic. The presence of lubricant coating may cause an increase in the disintegration time and a decrease in drug dissolution rate. The choice of a lubricant may depend upon the type of tablet being manufactured, dissolution, flow characteristics and requirements of the formulation in terms of hardness, friability and compatibility. Glidants are the materials that have good flow properties and poor lubrication properties.

     当润滑剂添加到粉末状材料中时,它们在每个微粒周围形成一个在压缩过程中或多或少能够保持完整的涂层。润滑剂大多是疏水性的。润滑剂涂层的存在可能导致崩解时间的延长和溶解速率的降低。润滑剂的选择可能取决于待加工片剂的类型、溶解性、流动性以及该配方对于硬度、易碎性和相容性的要求。助流剂是具有良好流动性和较差润滑性的材料。

     Glidants improve the flow of powder into the tableting machines for compaction. They act to minimize the tendency of a granulation to separate or segregate due to excessive vibration. High speed tablet machine require smooth even flow of material to die cavities (tablet mold). The uniformity of tablet weights directly depends on how uniformly the die cavity is filled. In general many materials commonly referred to as lubricants possess only a minimal lubricating activity and are better glidants or anti-adherents.

     助流剂能改善粉末进入压片机时的流动性,用来尽可能减小因振动过大而导致的颗粒分离或隔离的趋势。高速压片机要求片模腔中的物料流平滑均匀。片剂重量的均一性直接取决于对于片模腔的均匀填充。总之,许多通常被称为润滑剂的材料都是些只具有轻微的润滑性,反而是更好的助流剂或抗粘附剂。

     Thus a blend of two or more materials may be necessary to obtain these properties. Pharmacists should be familiar with the components of pharmaceuticals products, beyond their active ingredients. In order to educate pharmacists on excipients that are routinely used in the pharmaceutical industry, we decided to examine the top 200 prescription tablets and capsules products of 2003 (2) and find out how many or which excipients are used in each product.

     因此,为了获得这些性能,混合两种或两种以上的物质,也许是必须的。药剂师应该熟悉药品中的所有组分,而不仅限于其活性组分。为了让药剂师了解在制药行业中药用辅料的常规使用方法,我们决定对于2003年处方数前200位的片剂和胶囊品种进行调研,从中找出常用的有哪些辅料以及每一种药品中用了哪些辅料。

     The selection will cover both brand and generic drugs. Out of the 200 prescription drugs, the total numbers of inactive excipients used except for coating and coloring agents were ONLY 94! Although the list is composed on the top 200 drugs of 2003, very few blockbusters has been launched since then and still the excipients in all remains the same.

     这个调研结果既包括了品牌药,也包括了通用名药。除了涂层剂和着色剂外,200种处方药中用到的药用辅料的总数仅为94种!尽管下表只是由2003年的处方数前200位的药品中得来的数据,但从那以后很少再有重磅炸弹级的药品出现,而且所用的辅料也了无变化。

    

    

    

    

    

    

    

     From the table above we see that most of the commonly used ingredients have not been changed in making a tablet from generations and might follow the same trends for many generations to come.

     由上表可知,年复一年,在药品片剂生产中的常用辅料无多大变化,也许未来许多年仍会保持同样的趋势。

     CONCLUSION: Lot of time and effort are still needed in field of excipients. However till then a formulation scientist is entrusted with the limited amount of excipients and will have to deal with 94 excipients or now maybe 104.

     结论:在药用辅料领域仍然需要花费许多时间和精力。药品配方科学工作者以往曾与这有限数量的辅料打交道,今后仍然不得不面对这区区94种辅料,现在或许已经增加到104种。新闻来源:Drug Topic

    

    

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