A non-linear modelling approach to predict the dissolution profile of extended-release tablets.

Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
PMID:

Abstract

This study proposes a novel non-linear modelling approach to predict the dissolution profiles of extended-release tablets, by combining a full-factorial design, curve fitting to the dissolution profiles, and artificial neural networks (ANN), with linear regression methods, partial least squares (PLS) and multiple linear regression (MLR) as benchmarks. Hydroxypropylmethylcellulose (HPMC) and carboxymethylcellulose (CMC) grades, active pharmaceutical ingredient (API) lubrication, and compression force were chosen as DoE factors. The resulting batches were tested to obtain their corresponding dissolution profile, and a first-order dissolution equation was fitted to each profile. ANN, PLS and MLR were used to model and predict the tablet-specific constant k which then served to simulate dissolution profiles. This study demonstrates how non-linear methods, specifically ANN, outperform traditional linear models in predicting the complex interactions affecting drug release from extended-release formulations.

Authors

  • Ana Sofia Lourenço
    Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Professor Gama Pinto, 1645-003, Lisboa, Portugal. Electronic address: ana-lourenco@campus.ul.pt.
  • Tobias Schuster
    Global Analytical Technology Lab, Merck Healthcare KGaA, Frankfurter Straße 250, 64289, Darmstadt, Germany.
  • João Almeida Lopes
    Research Institute for Medicines (imed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Professor Gama Pinto, 1645-003, Lisboa, Portugal.
  • Annette Kirsch
    Global Analytical Technology Lab, Merck Healthcare KGaA, Frankfurter Straße 250, 64289, Darmstadt, Germany.