(724b) Towards a Generic Model for Twin-Screw Wet Granulation: Linking Material Properties to PBM Parameters.

Recently, the pharmaceutical industry has changed to produce solid oral dosages from the traditional inefficient and expensive batch production to continuous methods. In this context, the twin-screw wet granulator (TSWG) has become a promising wet granulation technique for continuous manufacturing of solid dosage forms due to its advantages, such as design flexibility, short residence time, and throughput range [1]. In parallel, population balance modeling (PBM) has emerged as a powerful model-based tool not only to predict the output of the desired property but also to increase the understanding and the enhancement of continuous twin-screw granulation processes [2]–[4]. One-dimensional PBM is still widely used in pharmaceutical manufacturing that primarily tracks only one particle property at a time, partly due to the lack of suitable equipment capable of measuring two or more properties simultaneously and the lack of suitable multi-dimensional kernels that have taken into account the specific process or the available experimental data [5], [6].

Several models to simulate the twin-screw wet granulation process have been published [1], [2], [5], [7]–[12]. However, a complete or more generic model involving material properties, process parameters and screw configurations is, to the authors’ knowledge, not yet available in literature [13]. This work seeks to take the first steps to address the development of a generic model, which from an industrial perspective is desirable to reduce the number of experiments required to expedite the time to market for new products. A one-dimensional compartmental PBM for the twin-screw wet granulation process is presented to simulate the particle size distribution. Pure aggregation in the wetting zone and a combination of aggregation and breakage in the kneading zones are assumed as the primary phenomena in the granulator. The aggregation kernel in the wetting zone corresponds to a modification of the aggregation kernel originally presented in the work by Van Hauwermeiren et al., 2018 [14]. In particular, a strategy is applied to reduce the amount of unknown parameters of the model in each compartment using patterns detected from the collected experimental data reducing the complexity of the calibration process.

The PBM was calibrated for three different Active Pharmaceutical Ingredients (APIs) of different nature, both, hydrophilic and hydrophobic, at low and high concentrations. Then, six formulations were studied at different granulator process conditions (the granules analyzed in this study were produced in the high shear twin-screw wet granulator module of the ConsiGma-25 from GEA Pharma Systems, ColletteTM, Wommelgem, Belgium, continuous line). Subsequently, Partial Least Squares (PLS) models were built using the calibration results to predict the PBM parameters from the material properties and liquid-to-solid ratio conditions as inputs. This generic PBM for TSWG will greatly reduce the amount of material needed for experimentation and it can reduce the time-to-market and experimental product development costs for a new product.

Acknowledgments:

Pfizer Inc.

Janssen Pharmaceutica NV

UCB

References:

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