The use of model simplifications and scale-independent parameters for building a design space on the film coating process
Uporaba modelskih poenostavitev in od ravni neodvisnih spremenljivk pri postavitvi eksperimentalnega prostora za proces filmskega oblaganja tablet : doktorska disertacija

english

doktorska dela

2021

Univerza v Ljubljani, Fakulteta za farmacijo
(Obvezni izvod spletne publikacije)

The objective of the doctoral study was to develop scale-independent design space for the film coating process. We coated hygroscopic tablet cores with a moisture protective polyvinyl alcohol coating in order to protect the hydrolysable model drug substance from environmental moisture. Since we could not discover a universal approach for design space development, based on an overview of the current literature, we have outlined throughout this work, in our opinion, the most optimal approach: (1) We used scale-independent coating process parameters (product temperature, polymer dispersion droplet size and process relative humidity) as input variables for a face-centered central composite design. (2) We combined empirical as well as mechanistic modeling, and utilized model simplifications to quantitatively link the scale-independent parameters to scale-dependent ones (inlet air temperature, inlet air flow rate, inlet air humidity, coating dispersion spray rate, atomizing air pressure) in order to perform experiments. For elucidating the mechanisms, through which scale-independent parameters influence the product quality attributes, we selected the following responses: (1) The permeability of the film coating in order to assess film formation and consequently coating functionality in terms of moisture protection. (2) Water activity of film coated tablets (FCT) at the end of the spraying phase. Further, we correlated both responses with long-term stability results of FCT. Based on the obtained models and implementation of the proper constraints on responses, we determined a complete sequence of design spaces, connecting scale- independent spaces with scale-dependent ones. The main findings are the following: (1) Model simplifications and hybrid modeling can adequately describe the coating process and could be used for building a design space, which is independent of manufacturing scale.(2) With scale-independent design space in the coating process, it is possible to efficiently predict, control, and optimize the long-term stability of a moisture sensitive product. (3) During the film coating process, humidity conditions play the most important role in achieving product quality. However, the moisture protective coating itself has a negative influence on product stability for packaging configurations with a desiccant, due to keeping the moisture inside the FCT and preventing the desiccant from effectively drying out the FCT.

12.05.2023