Shelf-life, extemporaneous preparations

An extemporaneous preparation is defined as a product which is dispensed immediately after preparation and not kept in stock [10]. Hence, many radiopharmaceuticals could fall into this category due to their limited shelf life. 

Emulsifying agents are used both to promote emulsification at the time of manufacture and to control stability during a shelf life that can very from days for extemporaneously prepared emulsions to months or years for commercial preparations. In practice, combinations of emulsifiers rather than single agents are used. The emulsifier also influences the in vivo fate of lipid parenteral emulsions by its influence on the surface properties of the droplets and on the droplet size distributions. For convenience, most pharmacy texts classify emulsifiers into three groups i) surface active agents ii) natural (macromolecular) polymers and hi) finely divided solids. 

Regarding Compatibility if components of a prescribed preparation are not compatible (or there is a lack of evidence), it does not mean automatically that it should not be prepared. The preparation needs to show sufficient compatibility up to the in use expiry date it may be possible to produce a preparation with a shortened but useful shelf life. Interactions between the active substances and excipients can however make it impossible to produce a preparatiOTi of sufficient quality. These incompatibilities can be visible or invisible during preparation. The attending pharmacist has to verily if incompatibilities are apparent. More informaticHi about incompatibilities is to be found in references such as Fiedler (Sect. 39.2.2), Handbook of Pharmaceutical Excipients (Sect 39.2.3), Martindale (Sect. 39.2.4), Handbook of Extemporaneous Preparation (Sect. 39.4.6), Konunentar zum Arzneibuch (Sect. 39.4.8) and Trissel s Stability of Compounded Formulations (Sect. 39.4.14). 

For non-standard extemporaneous pharmacy preparations, the design must include attention to the way of storage, and the maximum shelf life and beyond-use period after opening. For preparations with uncertain or xmknown... 

To get an idea of the stability of an extemporaneous preparation the only possibility is to keep a part of the preparation in the pharmacy in order to be able to recall if necessary or to have some information in case of a second prescription. For background information on the instability of disperse systems (suspensions, emulsions) and the ways to overcome those stability problems, see Sect. 18.4. For a useful review about the changes in dissolution rate during shelf life and how to prevent them, reference is made to [4]. 

Extemporaneous preparations, with unknown or uncertain chemical or physical stability, carmot be kept on stock in the pharmacy. They have a maximum usage period according to Table 22.15, but this period is not more than 1 month for liquid and semisolid preparations, and not more than 6 months for dry forms. If the formula is similar to a standardised one, the maximum shelf life of that standardised formula can be used. 

In separate sections the importance of choosing and defining relevant quality parameters to guarantee the required quality of the medicine is discussed. It is explicitly mentioned that stock preparations are generally tested more extensively than extemporaneous preparations. It is also mentioned that if it is not practical to perform tests on pharmacy preparations, for example because the batch is too small or because of the delivery time, other suitable methods may be used to guarantee that the required quality level is met. With this, the process validation has obtained an official position next to the end control of products. It should be stressed, however, that when tested at any point during the product shelf life the product must meet the specification in the monograph. 

---