Abdelhakim, Hend

Coupe, Alastair

Craig, Duncan

Edirisinghe, Mohan

Tuleu, Catherine

English

UCL Discovery

Manufacturing optimisation of electrospun Eudragit®E PO using a factorial designHend Abdelhakim,*1, Catherine Tuleu1, Alastair Coupe2, Mohan Edirisinghe3 and Duncan Craig1 Introduction 1University College London (UCL), School of Pharmacy, 29-39 Brunswick Square, London, UK, 2Pfizer Limited, Global R&D, Sandwich, Kent, UK and 3UCL, Department of Mechanical Engineering, Torrington Place, London, UK. * hend.abdelhakim.16@ucl.ac.ukReference:1. Hu, X. et al., 2014. Electrospinning of polymeric nanofibers for drug delivery applications. Journal of Controlled Release, 185(1), pp.12–21. ConclusionResults & DiscussionMaterials & Methods  E-EPO was donated by Evonik (Darmstadt, Germany). Allsolutions were prepared to 100% using absolute ethanol.Spraybase® electrospinning apparatus was used to manufacturethe fibres. A Scanning Electron Microscope (SEM) FEI Quanta200FEG, was used to image the fibres. ImageJ 1.46R was usedto measure diameters. JMP Pro 12.0.1 was used to create thefractional design and for data analysis. Parameters investigatedand their different levels are shown in Table 1.If a systematic approach was used to run experiments for allcombinations of the five chosen factors at three levels for each,this would have resulted in 35, or 243 separate experiments. Thefactorial design allowed for optimisation with only 14. These wereperformed over two different days. The temperature rangedbetween 23.5 – 24oC and the relative humidity (RH) rangedbetween 27 – 28 %.We describe a factorial approach that allows both theidentification of the most influential manufacturing conditions fornano-diameter fibres and absence of beading as well as theprediction of optimal conditions for both outcomes. The study hastherefore not only suggested parameters for producing E-EPOfibres but has also developed an approach for the rational choiceof electrospinning conditions.Fig. 2 - SEM image of 45% E-EPO, in 20%Water, processed at 16 kV, gap distance of150 mm and flow rate of 0.5mL/h, Meandiameter = 2789 nmFig. 3 - SEM image of 25% E-EPO, in 0%Water, processed at 25 kV, gap distance of250 mm and flow rate of 2mL/h,. Meandiameter = 416 nm , beading = 150/ 3 mm2Process • Voltage• Flow rate• Working distance• Collector type• Needle diameter Solution • Polymer concentration• Solvent• Electrical Conductivity• Viscosity• Surface TensionEnvironmental• Humidity• Temperature Electrospinning is used to manufacture nanofibres for variousapplications, including drug delivery. The fibres produced areaffected by a number of parameters, shown in Fig. 1:The aim of this study is to optimise the manufacturing of Eudragit®E PO (E-EPO), Poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate) 1:2:1 fibres by varying anumber of parameters using a definitive screening, fractionalfactorial design. This is the first electrospinning study of E-EPO forthe purpose of producing a taste-masked paediatric oral dosageform.Factor Low Medium HighApplied voltage (kV) 10.00 17.50 25.00Flow rate (mL/h) 0.50 1.25 2.00Gap distance (mm) 150.00 200.00 250.00E-EPO concentration (%w/v) 25.00 35.00 45.00Water in solvent (%v/v) 0.00 10.00 20.00Increasing polymer concentration was found to be the mostsignificant factor (p = 0.004) in producing non-beaded fibres. Theother parameters were not statistically significant; p values areshown in Table 2. Examples of fibres are shown in Fig. 2 and Fig.3.Table 1 - A table displaying the factors and the three corresponding levels for eachTwo criteria were set as the desired outcomes:1. Reduce fibre diameter to nano-range.2. Minimise beading.Minimising beading Minimising diameter Minimising fibre diameter was most affected by a decrease inpolymer concentration (p = 0.008). The significance of the otherparameters is shown in Table 2. The optimum parameters werepredicted to be 28% E-EPO, 20% water, flow rate of 0.5 mL/h,voltage of 25kV, and distance of 150 mm to generate fibres withan average diameter of 155nm, R2 = 0.92. Experimentalvalidation produced non-beaded fibres with an average diameterof 930 nm ( ± 348).As well as identifying key parameters, the factorial approach canalso be used to predict optimum conditions. For bead-free fibres,these were predicted to be 45% E-EPO, 20% water, flow rate of0.9 mL/h, voltage of ~21 kV, and distance of 150 mm, with an R2of 0.93. This was validated experimentally, thereby lending weightto the predictive approach.Table 2 - Statistical significance of different parameters on reducing beading & diameterOptimisation - When both outcomes were modelled together, theprediction profiler tool, shown in Fig. 4, predicted that at 25kV,35% E-EPO, 0.5mL/h flow rate, distance of 150mm, and additionof 20% water, fibres with an average diameter of 621 nm will beformed. They will also contain 37 beads per 3 mm2 (i.e. very lowbeading). When validated experimentally non-beaded fibres withan average diameter of 1508 nm (± 250 ) were formed .Fig. 1 - Interdependent parameters that may influence electrospinning 1Fig. 4 - Prediction tool showing the relationship between the parameters and outcomes.Effect on beading p Effect on diameter pConcentration 0.004 Concentration 0.008Flow rate 0.180 Voltage 0.220Distance 0.700 Water addition 0.260Water 0.764 Distance 0.641Voltage 0.778 Flow rate 0.820

Manufacturing optimisation of electrospun Eudragit® E PO for paediatric oral drug delivery

https://discovery.ucl.ac.uk/id/eprint/10153604/2/Abdelhakim_Hend_Abdelhakim_ULLA__POSTER_2017-%20UPDATED%5B11517%5D.pdf

Manufacturing optimisation of electrospun Eudragit® E PO for paediatric oral drug delivery

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