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An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System

The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and...

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Autores principales: Manda, Arthur, Walker, Roderick B., Khamanga, Sandile M. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470535/
https://www.ncbi.nlm.nih.gov/pubmed/30866418
http://dx.doi.org/10.3390/pharmaceutics11030109
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author Manda, Arthur
Walker, Roderick B.
Khamanga, Sandile M. M.
author_facet Manda, Arthur
Walker, Roderick B.
Khamanga, Sandile M. M.
author_sort Manda, Arthur
collection PubMed
description The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and dissolution studies were performed using United States Pharmacopoeia (USP) Apparatus 2 as described in USP XXIV. Analysis of dissolution test samples was performed using a reversed-phase high-performance liquid chromatography (RP-HPLC) method. Four formulation and process variables viz., microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed were investigated and drug release, aspect ratio and yield were monitored for the trained artificial neural networks (ANN). To achieve accurate prediction, data generated from experimentation were used to train a multi-layer perceptron (MLP) using back propagation (BP) and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) 57 training algorithm until a satisfactory value of root mean square error (RMSE) was observed. The study revealed that the in-vitro release profile of prednisone was significantly impacted by microcrystalline cellulose concentration and sodium starch glycolate concentration. Increasing microcrystalline cellulose concentration retarded dissolution rate whereas increasing sodium starch glycolate concentration improved dissolution rate. Spheronization time and extrusion speed had minimal impact on prednisone release but had a significant impact on extrudate and pellet quality. This work demonstrated that RSM can be successfully used concurrently with ANN for dosage form manufacture to permit the exploration of experimental regions that are omitted when using RSM alone.
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spelling pubmed-64705352019-04-27 An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System Manda, Arthur Walker, Roderick B. Khamanga, Sandile M. M. Pharmaceutics Article The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and dissolution studies were performed using United States Pharmacopoeia (USP) Apparatus 2 as described in USP XXIV. Analysis of dissolution test samples was performed using a reversed-phase high-performance liquid chromatography (RP-HPLC) method. Four formulation and process variables viz., microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed were investigated and drug release, aspect ratio and yield were monitored for the trained artificial neural networks (ANN). To achieve accurate prediction, data generated from experimentation were used to train a multi-layer perceptron (MLP) using back propagation (BP) and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) 57 training algorithm until a satisfactory value of root mean square error (RMSE) was observed. The study revealed that the in-vitro release profile of prednisone was significantly impacted by microcrystalline cellulose concentration and sodium starch glycolate concentration. Increasing microcrystalline cellulose concentration retarded dissolution rate whereas increasing sodium starch glycolate concentration improved dissolution rate. Spheronization time and extrusion speed had minimal impact on prednisone release but had a significant impact on extrudate and pellet quality. This work demonstrated that RSM can be successfully used concurrently with ANN for dosage form manufacture to permit the exploration of experimental regions that are omitted when using RSM alone. MDPI 2019-03-07 /pmc/articles/PMC6470535/ /pubmed/30866418 http://dx.doi.org/10.3390/pharmaceutics11030109 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Manda, Arthur
Walker, Roderick B.
Khamanga, Sandile M. M.
An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System
title An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System
title_full An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System
title_fullStr An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System
title_full_unstemmed An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System
title_short An Artificial Neural Network Approach to Predict the Effects of Formulation and Process Variables on Prednisone Release from a Multipartite System
title_sort artificial neural network approach to predict the effects of formulation and process variables on prednisone release from a multipartite system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470535/
https://www.ncbi.nlm.nih.gov/pubmed/30866418
http://dx.doi.org/10.3390/pharmaceutics11030109
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