An Integrated Modeling Approach for Studying Coated Tablet Dissolution Process
H. Wu1 , A. S. Hussain1 , M. A. Khan2 , R. C. Lyon2 , R. Voytilla3 , J. K. Drennen3 , 1CDER, Rockville, MD, 2CDER, Silver Spring, MD, 3DCPT at Duquesne University, Pittsburgh, PA
Background: In the current modeling practice of PAT domain, much attention has been paid to the multivariate modeling due to its capability of relating on-line measurement of quality attributes of final dosage forms to some of the formulation and processing parameters. While this may be exciting to the pharmaceutical community due to its convenience and non-destructiveness, the drawbacks of the soft modeling approach are easily overlooked. If not supported by other complimentary modeling approach, soft modeling approach alone could give misleading directions and the risk of extrapolating model for process control could be a reality.
Methods: An integrated modeling approach for studying coated tablet dissolution process was proposed. Soft modeling was applied to relate the tablet NIR spectroscopy data to the coated tablet dissolution data, without considering the complicated physical/chemical phenomena associated with the dissolution process. Then mechanistic modeling was applied to study the coated tablet dissolution process kinetics, taking account of the mass transfer phenomena.
Results: NIR predictions were linearly related to percent released across all studied formulations. The calibration correlation coefficients ranged from 0.87 to 0.99. The prediction errors from independent validation samples were <10% in most cases. However, the prediction quality degrades as dissolution time increases. A linear relationship was observed between the initial dissolution rates and coating levels, indicating Fickian diffusion may dominate the coated tablet dissolution process.
Conclusions: An integrated modeling approach may provide insights about the dissolution process behavior of coated tablets, thus a more reliable process control scheme becomes possible for PAT application.