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

Arthur Manda,Roderick Walker,Sandile Khamanga

doi:10.3390/pharmaceutics11030109

Arthur Manda, Roderick Walker + Show 1 more

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https://doi.org/10.3390/pharmaceutics11030109

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Journal: Pharmaceutics	Publication Date: Mar 7, 2019
Citations: 29	License type: CC BY 4.0

Affiliation: Rhodes University

Abstract

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.

Highlights

Prednisone is effective for treating certain types of arthritis, severe allergic reactions, multiple sclerosis, lupus and pathologies that affect the lungs, skin, stomach and intestines [1]
The objective of this work was to evaluate the impact of microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed on the in-vitro release of prednisone from a multiple-unit pellet system
The HPLC grade water used for analyses was prepared using a Milli-Q® Academic A10 water purification system (Millipore®, Bedford, MA, USA), consisting of an Ionex® ion-exchange cartridge and a quantum EX-ultrapore organex cartridge, which was fitted with a 0.22 μm Millipak® 40 sterile filter (Millipore®, Bedford, MA, USA)

Summary

Introduction

Prednisone is effective for treating certain types of arthritis, severe allergic reactions, multiple sclerosis, lupus and pathologies that affect the lungs, skin, stomach and intestines [1]. Prednisone is prescribed for serious pathologies such as cancer and as an adjunct to pneumonia therapy in patients with acquired immunodeficiency syndrome [2,3]. Regardless of all therapeutic benefits, the oral delivery of prednisone is associated with many challenges. Prednisone is a borderline Biopharmaceutics Classification System class I compound. Poor solubility and low dissolution rate in gastrointestinal fluids often result in low bioavailability [1]. Prednisone has harsh effects on the gastrointestinal tract (GIT) [5], in addition to an extremely bitter taste which needs to be masked to achieve better palatability [6]

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