Modeling the Dynamics of the Film Coating Operation for Pharmaceutical Tablets

Comprehensive Quality by Design in Pharmaceutical Development and Manufacture
AIChE Annual Meeting
October 29, 2012 - 1:00pm-1:15pm
Previous work in understanding the thermodynamics of the film coating operation has focused mainly around the pseudo-steady state reached between the drying air and the cooling effect from the evaporation of the spraying solution  [1]. The work presented here aims to mathematically describe the time-varying state of the operation and provide a structured procedure with the optimal experimental approach to estimate the heat and mass transfer coefficients across the system.
The ultimate objective of this work is to deliver a model able to predict the temperature of the tablets and the amount of water in the tablets during (and at the end of) the operation. Such a model will aid the design of the operating cycle for the film coating process if there were constraints on the maximum temperature/water activity that the tablet can be exposed to, or the final amount of water in the tablet core. Such constraints are not uncommon in water sensitive products since this can accelerate degradation mechanism and limit the shelf life of the product.
To obtain a model that is accurate enough (given the uncertainties in the measurements); mass and energy balances were calculated around: drying air, nozzle air, liquids and solids in the solution, tablet cores and equipment.  The model is implemented and all parameter estimations done using the gPROMS (Process Systems Enterprise Ltd, London, UK) modeling platform.
A key component to the model is the phenomena occurring at the surface of the tablet; that determines whether the water available in the impacting droplet is absorbed by the tablet or evaporated into the air. This mechanism is modeled as a function the thermodynamic state of the droplet as well as the hygroscopicity of the formulation, mass and surface area of the tablet, the vapour transmission properties of the coating solution and the extent of coating coverage in the tablet. The thermodynamic state of the droplet at the point of impact with the tablet is made dependent on the initial droplet size (calculated using rheological properties, nozzle geometrics, air pressure and the model by Aliseda et al [2]), the chemistry of the coating solution, the thermal conditions in the chamber and the distance traveled by the droplet (gun to bed distance).
The heat capacity of the equipment and the heat transfer from and to the equipment plays an important role to effectively model the energy transfer across the system (which in turn affects the prediction of temperatures). This is due to the fact that equipment becomes an energy sink that can absorb or emit energy in a non-linear way. These equations are established and coupled with the rest of the energy and mass transfer equations.
The model parameters are divided into those that characterize the equipment, the coating solution, the tablets and formulation, the tablet-gas mass and energy transfer and the tablet/liquid mass and energy transfer. Model-guided experiments are carried out in sequence to independently estimate each of the different interactions. The model is finally verified with 21 coating runs in an LDCS 20 coater using tablets of different sizes at multiple thermal conditions and extents of water exposure to the cores. The model is able to provide predictions well inside the experimental accuracy. 

References

 [1]  M.T.am Ende and A.Berchielli, A Thermodynamic Model for Organic and Aqueous Tablet Film Coating, Pharmaceutical Development and Technology, 10 (2005) 47-58.
 [2]  A.Aliseda, E.J.Hopfinger, J.C.Lasheras, D.Kremer, A.Berchielli, and E.K.Connolly, Atomization of viscous and non-newtonian liquids by a coaxial, high-speed gas jet. Experiments and droplet size modeling, International Journal of Multiphase Flow, 34 (2008) 161-175.

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