Application of artificial neural networks for Process Analytical Technology-based dissolution testing.

Journal: International journal of pharmaceutics
PMID:

Abstract

This work proposes the application of artificial neural networks (ANN) to non-destructively predict the in vitro dissolution of pharmaceutical tablets from Process Analytical Technology (PAT) data. An extended release tablet formulation was studied, where the dissolution was influenced by the composition of the tablets and the tableting compression force. NIR and Raman spectra of the intact tablets were measured, and the dissolution of the tablets was modeled directly from the spectral data. Partial Least Square (PLS) regression and ANN models were developed for the different spectroscopic measurements individually as well as by combining them together. ANN provided up to 3% lower root mean square error for prediction (RMSEP) than the PLS models, due to its capability of modeling non-linearity between the process parameters and dissolution curves. The ANN model using reflection NIR spectra provided the most accurate predictions with 6.5 and 63 mean f and f values between the computed and measured dissolution curves, respectively. Furthermore, ANN served as a straightforward data fusion method without the need for additional preprocessing steps. The method could significantly advance data processing in the PAT environment, contribute to an enhanced real-time release testing procedure and hence the increased efficacy of dissolution testing.

Authors

  • Brigitta Nagy
    Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3, Hungary.
  • Dulichár Petra
    Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3, Hungary.
  • Dorián László Galata
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary. Electronic address: galata.dorian.laszlo@vbk.bme.hu.
  • Balázs Démuth
    Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Hungary.
  • Enikő Borbás
    Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Hungary.
  • György Marosi
    Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Hungary.
  • Zsombor Kristóf Nagy
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
  • Attila Farkas
    Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Hungary.