Dexamethasone-releasing cochlear implant coatings: application of artificial neural networks for modelling of formulation parameters and drug release profile

Abstract

Over the past few decades, mathematical modelling and simulation of drug delivery systems has been steadily gained interest as a focus for academic and industrial attention. Here, simulation of dexamethasone (DEX, a corticosteroid anti-inflammatory agent) release profile from drug-eluting cochlear implant coatings is reported using artificial neural networks. The devices were fabricated as monolithic dispersions of the pharmaceutically active ingredient in a silicone rubber matrix. A two-phase exponential model was fitted on the experimentally obtained DEX release profiles. An artificial neural network (ANN) was trained to determine formulation parameters (i.e. DEX loading percentage, the devices surface area and their geometry) for a specific experimentally obtained drug release profile. In a reverse strategy, an ANN was trained for determining expected drug release profiles for the same set of formulation parameters. An algorithm was developed by combining the two previously developed ANNs in a serial manner, and this was successfully used for simulating the developed drug-eluting cochlear implant coatings. The models were validated by a leave-one-out method and performing new experiments. The developed ANN algorithms were capable to bilaterally predict drug release profile for a known set of formulation parameters or find out the levels for input formulation parameters to obtain a desired DEX release profile.