Abdelhakim, Hend

Coupe, Alastair

Craig, Duncan

Edirisinghe, Mohan

Tuleu, Catherine

English

UCL Discovery

Taste assessment of electrospun chlorpheniramine maleate fibres using an electronic taste sensing system Hend Abdelhakim1, Catherine Tuleu1, Alastair Coupe2, Mohan Edirisinghe3 and Duncan Craig1 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. Introduction Materials and MethodsAim• The primary aim of this study was to ascertain the detectability of the bitter taste of CPM by the e-tongue.• The secondary aim was to evaluate the taste masking effectiveness of electrospun CPM fibres.Bitter tasting medicines present a compliance barrier to thepaediatric population. Innovative techniques, such aselectrospinning, have the potential to mask the drug bitternesswhilst manufacturing an easy to swallow formulation. In this studychlorpheniramine maleate (CPM) was electrospun with the tastemasking polymer Eudragit E-EPO (E-EPO). The taste maskingefficiency of the manufactured fibres were assessed using anelectronic tasting system (E-tongue).Materials: E-EPO was donated by Evonik (Darmstadt, Germany). CPM was purchased from Cambridge Bioscience (Cambridge, UK). Electrospinning: Solutions of E-EPO were prepared in absolute ethanol. Spraybase® (Cambridge, USA) electrospinning apparatus was used to manufacture fibres with 1:6, 1:7, and 1:8 drug to polymer ratios.Taste assessment: TS-5000Z (Insent Inc., Atsugi-shi, Japan)electronic tongue was used to assess the taste of the samples.• Pure CPM was tested at 5 different concentrations using theclinical dose as a guide (0.25, 0.5, 1, 2 and 4 mg/mL) .• Pure E-EPO, physical mixtures, placebo fibres, and CPM fibreswere all tested by dissolving the equivalent of 20 paediatricdoses (20mg) in 100mL of 10mmol KCl solution, used as a supporting electrolyte. The mixture was then stirred for 1 minute at 37oC before being filtered out and tested.Data analysis: All experiments were run in triplicate and Euclidean distances were calculated from cluster centres. OriginPro (Massachusetts, USA) 2017 was used to complete a multivariate principal component analysis (PCA).SampleEquivalent Amount (mg)Euclidean distance E-EPO CPMPhysical Mixture 1:6 120 20 4.1Physical Mixture 1:7 140 20 5.1Physical Mixture 1:8 160 20 5.4Active fibre 1:6 30% E-EPO 120 20 7.4Active fibre 1:6 40% E-EPO 120 20 7.5Active fibre 1:6 35% E-EPO 120 20 7.9Active fibre 1:8 35% E-EPO 160 20 9.0Active fibre 1:7 35% E-EPO 140 20 9.2Placebo fibre 1:6, 30% E-EPO 120 0 21.8Pure E-EPO 1:8 800 0 22.1Pure E-EPO 1:6 600 0 22.8Pure E-EPO 1:7 700 0 24.0Results and DiscussionCPM’s taste was found to be detectable by the E-tongue sensors,as a basic bitter tastant. Figure 1 shows a concentrationdependent response to CPM.Table 1 – Euclidean distances from drug loaded fibres, placebo fibres, physical mixtures, pure E-EPO, to pure CPM.PCA: Out of the four sensors,the basic bitterness receptorAC0, had an eigenvalue of3.8, equating to 95% ofvariance, and therefore wasresponsible for principalcomponent 1. AN0, thesecond basic bitternessreceptor , was responsible forprinciple component 2.Euclidean distances were calculated to determine the differencesbetween the pure drug, physical mixtures, placebo and drugloaded fibre. These values are shown in Table 1.0 2 4-150-100-50050100150200Mean Sensor Response (mV)Drug Concentration (mg/mL) AC0  AN0  C00  AE1Figure 1 – Analysis of sensor responses to various concentrations of CPM: AC0 –basic bitterness; AN0 – basic bitterness; C00 - acidic bitterness; AE1 – astringency.Figure 2 – PCA biplot of drug loaded fibres compared to their physical mixtures, placebo fibre, pure E-EPO and pure CPM.ConclusionsThe E-tongue is an appropriate method to test the taste of CPMand therefore CPM formulations. This is the first study to look attaste assessment of electrospun CPM with E-EPO. There is someindication that taste masking may be improved by electrospinningthe drug with E-EPO, compared to the physical mixture.Future work: Further dissolution studies can quantity the exactamount of drug release. Results obtained from the E-tongue canbe further verified using a human taste panel or using an animalmodel.The greater the Euclidean distance between the pure drug and theformulation, the greater the difference in taste, and hence the besttaste masking effect. Figure 2 shows a map adapted from thesensor responses for all the samples tested. As anticipated, pureE-EPO had the largest Euclidean distance from pure CPM. Drugloaded fibres had a larger distance than the physical mixture,indicating better taste masking. However, drug loaded fibresEuclidean distances’ were closer to the physical mixtures than theplacebo fibre, which may indicate some drug release.Acknowledgments -4 -2 0 2 4-1.0-0.50.00.51.0-0.5 0.0 0.5-1.0-0.8-0.6-0.4-0.20.00.20.40.60.81.0AC0AN0C00AE11mg CPM1:6 CPM, 30% E-EPO1:6 CPM, 35% E-EPO1:6 CPM, 40% E-EPO1:7 CPM, 35% E-EPO1:8 CPM, 35% E-EPO1:6 E-EPO1:7 E-EPO1:8 E-EPO1:6 PM1:7 PM1:8 PM1:6 Placebo, 30% E-EPOPrincipal Component 2Principal Component 1Drug loaded fibresPure E-EPOPhysical mixturesPlacebo fibrePure CPM

Taste-assessment of electrospun chlorpheniramine maleate fibres using an electronic taste sensing system

https://discovery.ucl.ac.uk/10153602/1/2017%20Taste%20Assessment%20of%20CPM-%20EuPFI%20Poster.pdf

Taste-assessment of electrospun chlorpheniramine maleate fibres using an electronic taste sensing system

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