Materials Science: Solid Form Design and Crystallisation Process Development
Crystallisation is the final step of the active pharmaceutical ingredient (API) manufacture and so from a regulatory perspective must be both controlled and reproducible. In particular, it must provide an API of a suitable quality in terms of the purity and the appropriate physical properties for robust dosage form design and processing. In recent years a greater interest in the latter aspect has resulted in an emphasis of the link between the solid form, particle formation and formulation to be considered in a more integrated fashion. This has the associated benefits of streamlined API solid form selection, rapid commercial product design and intellectual property creation and product protection. In this chapter we have attempted to bridge the new cutting edge academic progress to the best industrial practices that crystallisation scientists can apply to advance new chemical entities consistent with the emerging quality by design landscape. The physical characteristics of the API ultimately have the potential to affect the safety, efficacy and manufacturability of the product being designed and manufactured. The emergence of a range of particle engineering technologies, coupled to state of the art characterisation technologies, has allowed access to a greater range of desirable particle attributes. Harnessing this capability to new sophisticated small-scale materials testing and institutionalised product design rules has led to the creation of a “design by first intent” strategy for API particles with tailored physicochemical attributes and functionality.