468412 Modelling Approaches to Spray Drying Process Development, Scale-up and Troubleshooting

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Pedro Valente1, Íris Duarte2, Filipe Neves3 and Márcio Temtem1, (1)R&D Drug Product Development, Hovione FarmaCiência SA, Loures, Portugal, (2)Faculty of Pharmacy, University of Lisbon & Hovione Farmaciência, SA, Loures, Portugal, (3)R&D Pilot Plant, Hovione FarmaCiencia, Loures, Portugal

Modelling approaches to spray drying process development, scale-up and troubleshooting

P.C. Valente, Í. Duarte, F.Neves & M.N. Temtem

1 R&D Drug Product Development, Hovione Farmaciência S.A, Sete Casas, 2674-506 Loures, Portugal;

Initiatives such as Quality by Design in the pharmaceutical industry have greatly increased the emphasis on physical and mathematical modelling of the various processes and the focus on science-based development [1]. The shift from the more traditional approach of the Quality by Testing is driven by the rational that better understanding of the underlying physical mechanisms leading up to the final dosage form leads to improved control of the quality of the final product and to accelerated product and process development. Spray drying of drug product intermediates is one of the pharmaceutical processes being shifted from Quality by Testing to Quality by Design and it is also illustrative of the various models that need to be developed in order to reach that goal. For example, when a spray drying process is employed to obtain an amorphous solid dispersion, an adequate understanding of the miscibility/phase separation between polymer and API can accelerate the screening of polymer candidates and optimized process conditions to ensure a homogeneous molecular dispersion between polymer and API. However, due to the complexity of the underlying physical mechanisms together with the fact that multiple physical phenomena are simultaneously at play, the task of creating an adequate model can be quite daunting. To overcome these difficulties it is crucial to have a pragmatic approach to modelling and to adequately formulate the problem statement so that no more complexity than absolutely necessary is fed into the model.

In this work we discuss five case studies where different levels of modelling are used, from statistical to first principles, to address product and process development needs as well as troubleshooting. In the first and second case-studies two models based on first principles are applied to the formulation of amorphous solid dispersions and to forecast the impact of particle design on the dissolution behavior. In the third and fourth case-studies two different levels of modelling, statistical and mechanistic, respectively, are applied to predict particle size of a spray dried powder based on the nozzle geometry, atomization and process parameters, showing that there is an unavoidable compromise between model accuracy and model generality. This case-study is also used to emphasize that the choice of model closely depends on the problem statement. A fifth case-study of troubleshooting a pharmaceutical process using computer fluid dynamics is also presented (Fig. 1).

Finally, the adequateness of the model complexity for tackling a given problem is discussed and two illustrative examples of overkilling or oversimplifying a model are given.

Figure 1: Troubleshooting example of a spray drying process using computer fluid dynamics. (Left) Gas velocity contours, (center) droplet spatial distribution within the drying chamber and (right) gas streamlines in the gas disperser and drying chamber of a spray drier.

References

[1] Lawrence X. Y. “Pharmaceutical Quality by Design: Product and Process Development, Understanding and Control”, Pharm. Res., 25 (4) 2008.


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