Abdelhakim, H

Coupe, A

Craig, D

Edirisinghe, M

Tuleu, C

English

UCL Discovery

Add your  Poster  NumberQR Code OnlyDEVELOPING SCIENCE. IMPACTING HEALTH.Electrospinning Optimisation of Drug-Loaded Eudragit E PO for PaediatricOral Drug DeliveryH. Abdelhakim 1, C.Tuleu 1, A. Coupe 2, M. Edirisinghe 1, and D. Craig 11 University College London, 2 Pfizer LtdPURPOSECurrently there is a lack of age appropriate formulations. Liquids cantaste bad, and solids are difficult to swallow, leading to poor compliancein the paediatric population.Manufacturing a novel dosage form that is palatable and is easy toswallow could be made possible by using a novel technique such aselectrospinning. By combining a bitter drug, Chlorpheniramine Maleate(CPM), with a taste masking polymer, Eudragit E PO (E-EPO), tastemasked fibres can be manufactured.Increased polymer concentration was found to be the most significant factor in increasing placebo fibre diameter, p-value = 0.008, and decreasing beading, p-value = 0.004. Similar to placebo fibres, concentration was found to be the most influential factor affecting fibre morphology. At a concentration of 40% E-EPO, smooth ribbons were formed, however, needle clogging halted the smooth running of the electrospinning process Generally, the conditions for producing good drug-loaded fibres were the same as with placebo fibres, when the drug was added at a 1:6 ratio to the polymer. RESULT(S)Initially placebo fibres were optimised, as shown in Figs 1a, 1b and 1c.DoE modelling tool predicted optimum conditions that maximise desirability -35% E-EPO, 0.5mL/h flow rate , 150 mm gap distance, 15-20 kV applied voltage were predicted to form fibres with  an average diameter of 621 nm and minimal beading. When validated experimentally smooth non-beaded fibreswith an average diameter of 1508 nm  (± 250 ) were formed (Fig 1b).When the drug was added, the solution properties changed and hence re-optimisation was required. SEM images shown in Figs 21, 2b and 2c.METHOD(S)All solutions were prepared to 100% using absolute ethanol. Ratios of1:6 of CPM :E-EPO were used in the drug loaded fibres. Spraybase®electrospinning apparatus was used to manufacture the fibres. AScanning Electron Microscope (SEM) FEI Quanta 200FEG, was used toimage the fibres. ImageJ 1.46R was used to measure diameters. JMPPro 12.0.1 was used to create the fractional design and for dataanalysis. Parameters investigated are shown in Table 1.The desired fibres were manufactured with the morphology and ease ofoperation as the optimisation criteria, namely reducing beading, andfibre diameter.FUNDING This study is funded by MRC iCASE award No. 170156, and Pfizer Ltd. Award No. 173803REFERENCE[1] S.R. Coles, D.K. Jacobs, M.O. James, G. Barker, A.J. Clark, K. Kirwan, J. Stanger, N. Tucker, A design of experiment approach to material properties optimization of electrospun nanofibres, J. Appl. Polym. Sci. 117 (2010) 2251–2257. doi:10.1002/app.CONTACT INFORMATION:  Hend.Abdelhakim.16@ucl.ac.ukW3112OBJECTIVEElectrospinning is affected by process, solution and environmentalfactors [1]. The aim of this study is to utilise a design of experimentapproach (DoE) to efficiently optimise the quality of the fibres produced.Fig. 1c - SEM image of 45% E-EPO,in 20% Water, processed at 16 kV,gap distance of 150 mm and flowrate of 0.5mL/h, Mean diameter =2789 ± 677 nm. Temp : 24o, RH:27%Fig. 1a - SEM image of 25% E-EPO,in 0% Water, processed at 25 kV,gap distance of 250 mm and flowrate of 2mL/h,. Mean diameter =416 ± 359 nm , beading = 150/ 3mm2. Temp : 24o, RH: 27%Fig. 1b - SEM image of 35% E-EPO,in 20% Water, processed at 25 kV,gap distance of 150 mm and flowrate of 0.5mL/h. Mean diameter =1508 ± 250 nm. Temp : 28o, RH:36%Fig. 2b – SEM image of 35% E-EPO,in 0% Water, processed at 15 kV,gap distance of 175 mm and flowrate of 1mL/h,. Mean diameter =2360 ± 326 nm. Temp : 24o, RH:46%Fig. 2a – SEM image of 25% E-EPO,in 20% Water, processed at 20 kV,gap distance of 150 mm and flowrate of 1mL/h,. Mean diameter =265 ± 124 nm . Temp : 24o, RH:30%Fig. 2c – SEM image of 40% E-EPO,in 0% Water, processed at 10 kV,gap distance of 150 mm and flowrate of 0.5mL/h,. Mean diameter =3237 ± 0.667 nm. Temp : 23o, RH:34%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 20.00Table 1 - A table displaying the factors and the three corresponding levels for eachCONCLUSION(S)The fractional factorial DoE approach reduced the number of runs required to optimise the placebo fibres from 35 or 243 runs, to 12 runs. The design identified the most influential manufacturing conditions for nano-diameter fibres and absence of beading as well as the prediction of optimal conditions for both outcomes.  The study has therefore not only suggested parameters for producing E-EPO fibres but has also developed an approach for the rational choice of electrospinning conditions. 

Electrospinning Optimisation of Drug-Loaded Eudragit E PO for Paediatric Oral Drug Delivery

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Electrospinning Optimisation of Drug-Loaded Eudragit E PO for Paediatric Oral Drug Delivery

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