ABSTRACT
Today the production of pharmaceutical granules is still based on the batch concept. In the early stage of the development of a solid dosage form the batch size is small, e.g., for first clinical trials. In a later stage the size of the batch produced in the pharmaceutical production department may be up to a 100 times larger. Thus the scale-up process is an extremely important one. Unfortunately, in many cases the variety of the equipment involved does not facilitate the task of scale-up. During the scale-up process the quality of the granules may change. A change in granule size distribution, final moisture content, friability, compressibility, and compactibility of the granules may strongly influence the properties of the final tablet, such as tablet hardness, tablet friability, disintegration time, dissolution rate of the active substance, and aging of the tablet. In the following sections, the scale-up process is analyzed, taking into account mathematical considerations of scale-up theory [1], the search for scale-up invariants [2-5], the establishment of in-process control methods [6-9], as well as the design of a robust dosage form [10-13]. In this respect new concepts such as percolation theory [13] play an important role. Finally, a new concept concerning a quasi-continuous production line of granules is presented [14-20]. This concept permits the production of small-scale batches for clinical trials and of production batches using the same equipment. Thus scale-up problems can be avoided in an elegant and cost-efficient way.
