Pharmacy preparation 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. 

The amount of a pharmacy preparation requested can vary widely, depending on the indication and area for use. The pharmacist should assess whether the amount is right for the use (see Fig. 2.7), the length of the treatment and the shelf life. In some countries, there are systems for standardising amounts used in order to improve consistency of products and maximise efficiency in the pharmacy setting, hi addition in some countries the amounts are limited by the health insurance. 

Sodium sulfate is an example of multidose powder, which is used as laxative in case of intoxication the patient should take several grams. To make this preparation more patient-friendly, the required quantity of Sodium sulfate decahydrate can be weighed into a dry bottle, which basically makes it a divided powder. Prior to use, the required amount of water is added to dissolve the powder. This may be drme in the pharmacy or elsewhere by the patient or the caregiver. An advantage of a powder over an oral solution is that the preparation has a l(Mig shelf life without the need for a preservative. 

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... 

Shelf life of pharmacy preparations depends on the character and stability of the preparation and has a maximum of 3 years as is explained in Sect. 22.7.1. Generally, physically and chemically stable suppositories have an expiry date of 3 years after preparation, both in strips in a carton or without strip in a jar. It may be convenient to split up this period in 24 months in the pharmacy and 12 months for use by the patient. 

Non-sterile but preserved vaginal solutions may have a shelf life of 3 years after preparatiOTi, if prepared according to a standard formula and chemically and physically stable. Once opened by the patient, such vaginal solutions can be assigned an in-use period of 6 months. A concentrate diluted by the patient should be kept only 24 h after dilution. A non-standardised preserved preparatirai should not be stored in the pharmacy because the maximal shelf Ufe of say 1 month, may be reasonably needed by the patient. A diluted concentrate may be kept for 24 h after dilution. Unpreserved n(Mi-sterile vaginal solutions may have a shelf life of maximal 2 weeks and they have to be stored in a refrigerator. 

The shelf life of reconstituted parenterals prepared in the hospital pharmacy is to be determined by the responsible pharmacist (see Sect. 22.6). When Ucensed injection fluids are reconstituted and prepared for individual patients the shelf life is determined by evaluation of the physico-chemical stability and risk of microbiological contamination. Shelf life depends from a microbiological viewpoint on the risks associated with aseptic preparation and the results of validation studies performed under the pharmacy s specified aseptic preparation cmiditions (see Sect. 31.3.6). 

For many products prepared in hospital pharmacies or in instimtions such as blood banks, the batch size is too small (one or only a few units) or the shelf life is too short (<14 days) to perform a complete sterility test as described in pharmacopoeias. In such instances, such as with radiopharmaceuticals (see Sect. 15.6.7), the pharmacist has to rely on the aseptic precautions during preparation (see Sect. 31.6). The use of rapid microbiological methods (RMMs) may also be an alternative to test products with such short shelf lives. 

When performing stability studies on medicines to determine shelf-life and usage periods, it is shown that chemical degradation may be fairly predictable but shelf life and usage periods may be influenced by less predictable causes. Changes that can be observed by the patient offer another perspective. The last section of the chapter provides advice on storage conditions, shelf life and usage periods of pharmacy preparations. 

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]. 

For pharmacy preparations, limits of 90-110 % apply to the entire shelf life (see Sect. 32.6). As an example the shelf life of the Dutch standardised preparations in the FNA is based on a maximum content decline of 5 %. When 10 % decline would be allowed, the chance on the active substance content falling below the lower limit of 90 % would be unacceptably high. If setting the limit for decline of content at 5 % would result in unacceptable storage conditions or an unacceptably short shelf life, it can be reasoned to accept a decline of 10 %. 

The reduced reliability of the results of stability studies on pharmacy preparations compared to the stability data of licensed medicines can be compensated with a relatively short shelf life. 

Pharmacy preparations usually have a short shelf life therefore, sampling times should be adjusted accordingly. 

In the pharmacy, shelf life is often only based on a specific temperature. For licensed medicines shelf life may be traced from the product information by the manufacturer or investigated by the pharmacist for pharmacy preparations. Many situations in practice however require stability data at different temperatures, different concentrations, solvents or containers. A justified extension of a shelf life could be very helpful for the patient or the pharmacy s logistics as well as saving a lot of money. 

For each medicine the storage conditimis should be indicated, as well as the shelf life and the beyond-use-date after opening. In this section it is explained how storage times are determined in general. Secondly, a system is introduced that can be used especially for pharmacy preparations. Finally storage conditions are dealt with. 

A maximum of 5 years seems to be a sensible maximum shelf life or tum-around time for licensed medicines [89]. For pharmacy preparations the quality of design and of productirai is less well controlled than in industrial production. For this reason for pharmacy preparations a maximum shelf life of 3 years has become an acceptable limit in many Countries. But for many preparations the shelf life will be less than 3 years, because they are unstable in one way or another. 

Thus a great deal of pharmacy preparations will have a shelf life after opening that is shorter than in the intact package, for two main reasons. A relatively large part of pharmacy preparations are vulnerable to microbiological contamination, and caution in determining the shelf life is the consequence of the often limited amount of research on this subject. 

The shelf life of a pharmacy preparation is 3 years at maximum. 

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. 

For the control of the production of medicines quality requirements are essential. Quality requirements cover the quality of the preparation throughout the whole shelf life, from release until the end of the shelf life. Medicines that are produced by the industry or prepared in a pharmacy have to meet the requirements of the European Pharmacopoeia. Status, type and structure of its monographs are dealt with. This chapter explains what quality requirements are. Also the background to the general quality requirements such as identity and content are discussed. 

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. 

For a standardised preparation the product file may be quite extensive. There is need for a more elaborate evaluation of the topics discussed above, and the product file should also include information on the validation of the preparation and on the stability and shelf life of the preparation. The product file of pharmacy preparations that are distributed on a relatively large scale should be the most extensive. The various topics of the product file in its most extensive form will be discussed in detail in the following subsections. At the end of each section an example of 12.5 mg diclofenac suppositories is used, assuming that diclofenac is not available in this strength as licensed medicine. 

The Formularium der Nederlandse Apothekers (FNA) is a Dutch formulary that contains about 250 national standardised formulations on pharmacy preparations. Each formulation contains a qualitative and quantitative composition of the preparation, preparation method, the recommended packaging, storage conditions and related shelf life and quality requirements of the preparation. 

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