Product optimisation excipient selection

In conclusion, during product optimisation, excipients will be selected based on a variety of acceptance criteria. The quantities included in the formulation will be finalised, based on the performance characteristics of the excipient in the final product. At this stage it is important to fix the specifications of the excipients to ensure that the materials used, and hence the product, will be consistent throughout development. Setting specifications is discussed in a following section. 

To develop a product from inception to market, the product and process have to be optimised and the process scaled up and transferred to commercial production. Definitions and descriptions of the requirements for all these stages of development are discussed in Chapter 8, although the major discussion is on the preformulation/formulation input to product optimisation. The many factors which a formulator should consider in the selection of pharmaceutical excipients and packaging are discussed. Useful sources of information and techniques for selection such as expert systems and experimental design tools are included. 

At the early stages of optimisation, preformulation studies are usually conducted to screen excipients or packaging materials and to select those compatible with the candidate drug, using accelerated stress testing procedures. More details about the preformulation techniques, which can be employed for compatibility studies, are discussed in Chapter 3. The importance of doing compatibility studies is for reducing the number of excipients and formulation options to test in further product optimisation studies. 

At the completion of product optimisation, when the best product variant has been selected, it is a good idea to summarise the work conducted in a Product Optimisation Report. The report should reference the primary data from preformulation, product optimisation and stability studies, cross-referencing other investigational reports where necessary. It should clearly justify the recommendations for the quantitative formula and the excipient, component and product specifications. Such a document can be very useful to aid smooth technology transfer into production and for writing regulatory submissions. 

The final stage of optimisation will normally involve generating sufficient stability data on one or more variants to select the best variant. The optimal product will usually be selected based on technical merit. However, there may be a need to consider other factors, such as the use of novel excipients and the associated safety/toxicological implications, supplier and sourcing issues or the ability to patent the formulation or not. Some of these issues are discussed further below. 

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