(625g) Surrogate Modeling of Dissolution Behavior Toward Efficient Design of Tablet Manufacturing Processes
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Development of Pharmaceutical Processes for Drug Substance and Drug Product Manufacture
Thursday, November 19, 2020 - 9:15am to 9:30am
This work presents surrogate modeling of dissolution behavior for enhancing the use of first-principle modeling in the design of tablet manufacturing processes. Our research approach consists of the following three steps: (i) collect process input and output data using gPROMS, (ii) perform surrogate modeling, and (iii) test the developed model. In the first step, 200 data are collected per each manufacturing method by simulating flowsheet models. Secondly, random forests are used for developing surrogate models from collected data sets after fitting Weibull models for dissolution behaviors. Finally, in the third step, sensitivity analysis is performed using the developed surrogate model to generate a proposal for the efficient process design.
Case studies of dry granulation and wet granulation methods were performed, where paracetamol was used as an API of the tablets. The simulation results showed the differences in tablet properties between manufacturing methods, e.g., hardness, porosity, and dissolution. After the execution of surrogate modeling, the sensitivity of input parameters was assessed using rank correlation coefficients, which determined critical parameters in the process, and product design phases. In ongoing work, the generality and the effectiveness of the developed models are discussed by performing case studies using a different API.
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