Innovations in control of freezing in pharmaceutical processes

The freezing step determines the structure of the product and influences the following drying steps; spontaneous nucleation is a stochastic process, which leads to nucleation at different times and thus temperatures, which in turn affect the ice crystal size. In recent years attention focused on controlled nucleation, to force all vials to nucleate at the same time and at the desired temperature; this will allow to shorten the freezing step, to get a structure which larger pores, that will consent a more aggressive drying cycle, without increasing the product temperature, and thus can be considered a way of process intensification. The most interesting benefits consist in the better uniformity of the batch, anyway. In this chapter the most interesting techniques (ultrasounds, vacuum induced surface freezing, pressurisation-depressurisation, ice fog) will be revised, discussing the working principle, the advantages and limitations, considering also effects on dissolution rate and drug stability. Current industrial applications, and possibility of scale up and process transfer will be also discussed.