2006 AIChE Annual Meeting
(668d) Engineering Considerations on Modeling for Pharmaceutical Process Analytical Technology (Pat) Applications
In this work, two case studies are presented to illustrate how engineering principles and modeling tools can be utilized to enhance pharmaceutical process understanding and to help achieve Quality-by-Design from the product/process design perspective.
The first case study deals with the multivariate modeling of a tablet dissolution process. In conjunction with the multivariate statistical modeling, classical engineering principles of mass transfer and Fick's diffusion law were applied successfully to accomplish two goals: modeling the tablet dissolution process and identifying critical process variables for this process.
The second case study is based on the scale-up of a multi-phase agglomeration mixing system. It will illustrate how chemical engineering scale-up methodologies can be used to cope with the scale-up issues in mixing and agglomeration systems. In this case, the minimal time required to produce spherical agglomerates, tE , and final size of the agglomerates, dp, as measured by an off-line imaging system, were analyzed by applying a combination of multiple linear regression analysis and statistical analysis of variance to determine the dependence of tE and dp on the independent variables. Correlations were established to describe how processing parameters, such as power input per unit volume (P/V) and impeller tip speed (S), impact the process outcomes measured by tE and dp. By selecting a suitable scale-up rule, the mixing tank was scaled-up successfully by testing on three different tanks whose diameter ranged from 11.2 to 24.0 cm. The relevance of the chemical engineering scale-up methodologies as applied to pharmaceutical process understanding will be discussed.