ABSTRACT
INTRODUCTION Historically, many freeze-drying cycles have been arrived at on an empirical basis, and while some of these cycles may produce consistently acceptable products, in recent years it has become more widely accepted that cycles should be developed on a more rational and scientific basis with an understanding of the formulation in question (1,2). There is therefore a need to provide documentary evidence to support the rationale of how a formulation has been selected and the corresponding freeze-drying cycle has been developed on the basis of that specific formulation, particularly with regard to its critical temperature(s) and its response to freezing, sublimation, and desorption. This in turn has led to the advent of more commercially available equipment and methods, which together can provide a reasonably complete characterization of a material prior to freeze-drying, so that processing conditions may be selected on a case-by-case basis. In this volume, Wang describes a logical stepwise approach to formulation characterization for freeze-drying. In this chapter, we expand on some of the formulation parameters that are pertinent to achieving a freeze-dried product with acceptable appearance on the macroscopic and microscopic scales, aspects of which may be considered qualitative parameters that are difficult to assess. Secondly, we describe some of the more widely used, well-established methods that enable characterization of a formulation with a view to achieving structural integrity in the dried product and discuss some of the issues surrounding data interpretation and their relevance to freeze-drying. Thirdly, we outline some recent advances in this field with regard to new methodologies, and present and discuss some data from a novel method of electrical impedance analysis that may help understand how a formulation may behave at the microscopic level as it undergoes freeze-drying. Finally, we discuss some of the issues surrounding data interpretation from the various formulation characterization methods and their relevance to the development of a freezedrying cycle for a pharmaceutical or biological product.
