Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches.

Kazem Nazari,Zeeshan Ahmad,Omar Qutachi,Prina Mehta,Shahabuddin Ahmed,Eleftherios G Andriotis,Dimitrios G Fatouros,Muhammad Sohail Arshad,Ming-Wei Chang,Neenu Singh

doi:10.3390/pharmaceutics12010002

Abstract

The purpose of this study was to apply the Quality by Design (QbD) approach to the electrospinning of fibres loaded with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin (INDO) and diclofenac sodium (DICLO). A Quality Target Product Profile (QTPP) was made, and risk assessments (preliminary hazard analysis) were conducted to identify the impact of material attributes and process parameters on the critical quality attributes (CQAs) of the fibres. A full factorial design of experiments (DoE) of 20 runs was built, which was used to carry out experiments. The following factors were assessed: Drugs, voltage, flow rate, and the distance between the processing needle and collector. Release studies exhibited INDO fibres had greater total release of active drug compared to DICLO fibres. Voltage and distance were found to be the most significant factors of the experiment. Multivariate statistical analytical software helped to build six feasible design spaces and two flexible, universal design spaces for both drugs, at distances of 5 cm and 12.5 cm, along with a flexible control strategy. The current findings and their analysis confirm that QbD is a viable and invaluable tool to enhance product and process understanding of electrospinning for the assurance of high-quality fibres.

Highlights

Electrospinning is a one-step technique that yields fibres with diameters of micro- or nano-scale size
The Quality Target Product Profile (QTPP) is a predefined summary of the characteristics of the product that must be of appropriate quality to meet the patient’s requirements and be fit for purpose
It would be more preferable to perform electrospinning at 5 cm distance for both INDO and diclofenac sodium (DICLO), as the design spaces for both drugs is at their largest, giving more freedom to choose the parameter settings for the process

Summary

Introduction

Electrospinning is a one-step technique that yields fibres with diameters of micro- or nano-scale size. Many scientists have dedicated their research to this remit with respect to the uses of these fibres, and due to their many appealing characteristics, many applications have been established [2,3] These applications include biomedical engineering [4], imaging [5], specialised drug delivery systems [6], wound dressings and tissue engineering [7], and nano-encapsulation of bioactive compounds [8]. Technological developments to the electrospinning process have been studied, giving rise to new ways to produce the three-dimensional (3D) fibres [9] Examples of these include blend electrospinning [10], electrospinning using alternating current [11], and electrospinning using

Objectives

Methods

Results

Conclusion