ABSTRACT
I. INTRODUCTION Scale-up of a manufacturing process, referred to as process scale-up or process translation, involves the transformation of a small-scale process occurring in the laboratory or in a pilot plant to a large-scale process occurring in a production plant. Tatterson [1] notes that the ultimate purpose of process translation is to make a product in large, commercially useful quantities, thereby ensuring mass production, cash flow, wealth, and profit. Dale [2] emphasizes that the proper design and development of the scaleup process reduces the time to market and allows for more rapid commercialization of a product. Unfortunately, process scale-up from the bench or pilot plant to commercial production is not a simple extrapolation, particularly for disperse systems. Few guidelines for the formulator have been available, up until now, in the pharmaceutical literature [3]. As yet, there is no scale-up algorithm that permits us to rigorously predict the behavior of a large-scale process based on the behavior of a small-scale process [4]. This is due to the complexity of the manufacturing process, which involves more than one type of unit operation (e.g., weighing, mixing, transferring). The successful linkage of one unit operation to another defines the functionality of the overall manufacturing process. Each unit operation per se may be scalable, in accordance with a specific ratio, but the composite manufacturing process may not be, as the effective scale-up ratios may be different from one unit operation to another. Unexpected problems in scale-up are often a reflection of the dichotomy between unit operation scaleup and process scale-up. Furthermore, commercial production introduces problems that are not a major issue on a small scale: e.g., storage and materials handling may become problematic only when large quantities are involved; heat generated in the course of pilot-plant or production-scale processing may overwhelm the system's capacity for dissipation to an extent not anticipated based on prior laboratory-scale experience.
