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[有求必应] 求教：有关设置渗透压摩尔浓度检查项的几个问题

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henryyelei 发表于 2016-8-12 14:47:13 | 只看该作者回帖奖励

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同写意41期高扬老师关于注射剂的质量控制做了演讲，其中有关其提到的渗透压的问题，不太明白，请各位战友能够指点一二，弄清问题。

高扬老师关于注射剂渗透压的制定，其PPT是这样写的：

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查询ICHQ6A原文，有关渗透压的描述应该是这条：

k) Osmolarity: When the tonicity of a product is declared in its labeling, appropriate control of its osmolarity should be performed. Data generated during development and validation may be sufficient to justify performance of this procedure as an in-process control, skip lot testing, or direct calculation of this attribute.

这里的tonicity应该是渗透压的意思，不能理解为肌肉紧张吧，这段我觉得意思应该是如果标签上注明了渗透压，就要设置渗透压摩尔浓度这项检查。不知道各位战友是怎么理解的。另外日本要求肌注设置摩尔渗透压，静脉与皮下不要求，这个不知出自何处，在JP16中好像没有这样的表述，请教各位战友，是否有人知道出处。

下面是国外对tonicity的解释和JP16注射剂通则项下内容

国外对tonicity的解释

Tonicity and Osmotic Pressure

Tonicity is an important topic when we look to make parenteral products. As mentioned in the lecture, ideally an IV admixture is used in a solution that is isotonic to blood. The human body is made up of around 60 percent water so it is critical that tonicity is considered when making intravenous formulations. A drug solution that is hypertonic to blood could locally shrink cells and cause severe pain and problems administering the drugs where as hypotonic solutions can present problems as well causing cells to lysis and burst. As mentioned in PHCY 410, drugs that are hypotonic or hypertonic that must be administered should be done slowly to minimize the negative side effects, however; ideally we work to make drug admixtures in hospitals isotonic to blood when we intended to administer them in a parenteral fashion. Some of the most common modes of delivering near isotonic drugs into the body is by using normal saline (0.9% NaCl), 5% dextrose, and lactated ringers. Each of these roughly have a osmolarity of 270-300 mOsmol/L, which is on par with blood. The importance of which fluid you use in certain preparations is evident. Firstly, some drugs are much more stable in one or the other medium so it is important to note this when deciding how to administer a drug to a patient. Secondly, NaCl is an electrolyte and will display those properties when administered with a drug, where as dextrose is a non-electrolyte. Dextrose 5% can also act as a hypotonic solution as the dextrose is metabolized by the body. The lactate in lactated ringers are converted by the liver into bicarbonate, so this is an obvious consideration when developing an intravenous infusion and could be used when the patient needs increased levels of bicarbonate and should be avoided in patients whose blood pH is higher than 7.5 or if they have a severe liver disease and the lactate cannot be converted. Generally, drugs added to these isotonic solutions increase their tonicity. Different disease states and patient conditions can call for mixtures that are not isotonic to blood. In other cases many fluids used can be hypotonic or hypertonic and used in patient specific circumstances. Two common such fluids are 0.45% NaCl (hypotonic) and 10% dextrose (hypertonic). Another thing to notice when making an injectable product is the use of buffers when working to maintain these parenteral formulations. In addition to the tonicity and osmotic pressure issues when making parenteral products it is important to monitor the buffers used to make sure the product is safe for use in parenteral products. There are many different buffers that are effective in different ranges. Physiological pH in humans is a little over 7 so the most effective buffer used in formulations for humans is phosphoric acid or phosphate. These buffers are usually considered safe in formulations when it is used in the 2-30 mM range. This issue of pH is very important because even with buffer systems in the body in place, if the pH of the formulation is much higher or lower than physiological pH it can produce hazards to the body. With all of these parameters to consider it makes it very difficult to make drug formulations that adhere to these specific requirements.

JP16注射剂通则项下内容

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