Primary vial batch

Figure 21 Scale-up/down study in primary drying process of frozen LMOX solution (22%) regarding thermal deviations. Two types of freeze-dryers were used (—) 2000 vials/batch of experimental size (---) 60,000 vials/batch of commercial size (1) standard program to estimate a thermal deviation (2) optimized program as a result of scale-up/down studies.

The computer must determine the rate at which this step develops from the heat of sublimation of the ice in the sample and the uncrystallized water present in the interstitial region. Also, it should take into account the heat transfer coefficient of the sample container — in the case of a vial, not just a single container, but the frequency distribution of an entire lot of containers. From this statistical information, the computer can then determine the highest shelf-surface temperature where, based on knowledge of the batch size, the chances that the heat transfer coefficient of a container would result in a product temperature exceeding the collapse temperature and yielding a defective product are minimal. The frequency distribution of the heat transfer coefficients of the containers would also provide the computer with the information needed to extend the primary... 

Quantitative and (hopefully, at least) qualitative considerations are helpful in characterizing a liquid-liquid system for a potential extraction application. Batch shakeout tests are frequently the easiest way to determine basic feasibility by simply measuring the primary and secondary break times and by analyses to measure the compositions of the equilibrated phases. Such tests are readily conducted by mixing small volumes of each phase in a vial, which is then vigorously agitated and placed on a lab bench to settle. The resulting behavior of the liquid-liquid mixture depends on physical properties and system characteristics. The greater the density difference and interfacial tension between the two liquid phases, for example, the more rapidly the phases tend to separate. More viscous systems separate more slowly. 

From experience, most radiopharmaceutical kits dried at 4-10 °C result in final products of good quality. For example, a batch of 1000 vials (volume = 2 ml) requires a 24-h primary drying cycle (4-10 °C), followed by another 24-h secondary drying cycle. 

The various techniques available to monitor the primary drying can be roughly divided into three groups as they can be used to monitor single vials, a group of vials or the whole batch (Barresi et al, 2009a) these techniques will be discussed and compared in the following sections. 

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