Abstract
The pharmaceutical tablet manufacturing process (PTMP) via wet granulation holds a critical position in pharmaceutical industry. The interest in integrating mechanistic process modeling into the pharmaceutical development has been increased because simulation model is a prerequisite for process design, analysis, control, and optimization. So the simulation modeling for PTMP via wet granulation is very necessary and significant. This study aims at proposing a simulation modeling framework for PTMP via spray fluidized bed granulation (SFBG), which is one of the most widely used wet granulation techniques in pharmaceutical industry. For SFBG, a simulation model that simultaneously involves the influences of operating variables and material attributes on average particle size (APS) is firstly developed, and then a drying model to determine the particle moisture content is introduced to be coupled with the established model predicting APS. For PTMP, considering the important effect of porosity on tablet qualities, a model describing the changes in tablet porosity is developed based on a promoted form of the Heckel equation, and then several recognized models that are all related to porosity are introduced or constructed to calculate important tablet quality indexes. The feasibility and effectiveness of the developed simulation models are validated by performing a computational experimental study to explore the scientific understanding of process and process quality control.
Highlights
Oral dosage forms, such as tablets, account for the most popular drug delivery systems for treating patients today [1,2,3]
The feasibility and effectiveness of simulation models are tested through a computational experimental study—simulations. e influences of process parameters and material attributes on the intermediate or final quality attributes are firstly studied by implementing simulation experiments, whose results are compared with the widely accepted conclusions in the field. e feasibility and effectiveness will be confirmed by the consistencies of simulation results and recognized analysis or conclusions
In order to verify the effectiveness of simulation models in process quality control, a validated control method is applied to determine whether the simulated SFBG-based pharmaceutical tablet manufacturing process (PTMP) can be used for designing or testing control algorithms
Summary
Oral dosage forms, such as tablets, account for the most popular drug delivery systems for treating patients today [1,2,3]. To the authors’ knowledge, research studies on simulation modeling for such an integrated process, i.e., PTMP via wet granulation, are very limited and mainly focused on continuous tablet manufacturing [5, 10]. E primary aim of the present study is to develop a simulation modeling framework which can link the key operating variables and material attributes with the properties of granules or tablets to predict the granulation and tabletting behavior in the SFBG-based PTMP. Once the actual experimental data are available in the future studies, the modeling framework can be identified and validated with the actual process data to make it practical for simulation, which is important for intending to use the models as a tool for the pharmaceutical Quality by Design.
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