Determination of Design Space for Oral Pharmaceutical Drugs

Kaliopi Chatzizacharia Dimitris Hatziavramidis1
School of Chemical Engineering, National Technical University of Athens, Zografos 15780 GR

1corresponding author dthatzia@central.ntua.gr

Within existing regulatory framework any type of change in formulation or process conditions in manufacturing pharmaceutical products, however small, requires regulatory approval. Under the new Quality by Design (QbD) initiative, however, it is possible to use knowledge from development studies to create a Design Space (DS) within which changes in formulation and manufacturing processes promoting continuous improvement of process capability and product quality can be implemented without the need for further regulatory approval.
Methodologies to determine the Design Space of oral pharmaceutical drugs, within which continuous improvement can be implemented and post-approval changes in material attributes and process parameters can be introduced without prior approval, are presented. These methodologies, which proceed along the overlapping responses and multiple-response optimization paths, are applied to two examples. The first example involves two- and three-stage tablet making with response variables the tablet weight, strength and disintegration time and factors the amount of moisture, the powder flow rate and the compression force. In the second example, responses are tablet weight, hardness and dissolution profile, and factors excipient weight fractions.