Pharmaceutical manufacturing typically lags behind other industries in process efficiencies because production processes for new drug products are quickly developed in a laboratory for producing clinical-trial materials to enable the rapid submission of a new drug application (NDA) (1). The NDA locks in the documented manufacturing steps with a regulatory commitment and leaves no chance for the full optimization of processing steps such as crystallization, filtration, drying, dry blending, granulation, drying, and tableting (2). Granulation is the slowest of these processing steps, but by applying cross-performance relationships and mixing rules, the efficiency of granulation can be enhanced significantly (2-4). To achieve lean solid-dose manufacturing, the granulation step can be replaced with spherical crystallization in a common stirred tank at the crystallization step (5-26). This change may reduce the time-consuming and labor-intensive steps in solid-dose manufacturing for a high-dose formulation to only a few unit operations of spherical crystallization, filtration, drying, dry blending, and tableting.
Pharmaceutical Technology, Mar 2, 2010