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Chiang Mai J. Sci. 2015; 42(2) : 469-480 http://epg.science.cmu.ac.th/ejournal/ Contributed Paper Formation of Orally Fast Dissolving Fibers Containing Propolis by Electrospinning Technique Chawalinee Asawahame [a], Krit Sutjarittangtham [b], Sukum Eitssayeam [b], Yingmanee Tragoolpua [c], Busaban Sirithunyalug [a] and Jakkapan Sirithunyalug*[a] [a] Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand. [b] Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand. [c] Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand. *Author for correspondence; e-mail: [email protected] Received: 15 March 2013 Accepted: 11 July 2013 ABSTRACT The objective of this study was to prepare orally fast dissolving fibers using the electrospinning process with hydrophilic polymers. Polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) were chosen as the fiber-forming polymers and propolis was used as the active ingredient for antibacterial property in the fibers. Morphology of electrospun fibers was influenced by solution parameters (viscosity, conductivity, surface tension) and process parameters (electric field strength, flow rate, collector type). This investigation used different types and molecular weights of polymers (PVP K90, PVP K30, PVA MW 85,000-146,000 and PVA MW 47,000) to influence the spinnability of the polymer solution and so the morphology of the electrospun fibers. It was found that PVP K90 at 8-10% (w/v) in ethanol and PVA MW 85,000-146,000 at 10% (w/v) in deionized water produced electrospun fibers with appropriated quality and stability. Ethanol and deionized water were used as a mixed solvent to study the effect of co-solvent on fiber morphology. The results showed that increasing another solvent in the polymer solution changed the morphology of electrospun fibers and affected the stability of electrospun fibers. Incorporated propolis (2% w/v) and small amount of additives into PVP K90 (8% and 10% w/v) nanospun fibers gave smooth and uniform fiber morphology with diameters ranging from 0.55-0.95 μm and produced fiber mats which wetted and dissolved rapidly in water within 10 seconds. Keywords: electrospinning, fast dissolving fibers, propolis, polyvinyl pyrrolidone, polyvinyl alcohol 1. I NTRODUCTION Electrospinning is one technique that uses electrohydrodynamics for producing fine fibers by electrostatic forces. Fibers from this technique have small diameters ranging from nanometers to micrometers. The term electrospinning is derived from electrostatic

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Chiang Mai J. Sci. 2015; 42(2) 469

Chiang Mai J. Sci. 2015; 42(2) : 469-480http://epg.science.cmu.ac.th/ejournal/Contributed Paper

Formation of Orally Fast Dissolving Fibers ContainingPropolis by Electrospinning TechniqueChawalinee Asawahame [a], Krit Sutjarittangtham [b], Sukum Eitssayeam [b],Yingmanee Tragoolpua [c], Busaban Sirithunyalug [a] and Jakkapan Sirithunyalug*[a][a] Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University,

Chiang Mai 50200, Thailand.[b] Department of Physics and Materials Science, Faculty of Science, Chiang Mai University,

Chiang Mai 50200, Thailand.[c] Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.*Author for correspondence; e-mail: [email protected]

Received: 15 March 2013Accepted: 11 July 2013

ABSTRACTThe objective of this study was to prepare orally fast dissolving fibers using the

electrospinning process with hydrophilic polymers. Polyvinyl pyrrolidone (PVP) and polyvinylalcohol (PVA) were chosen as the fiber-forming polymers and propolis was used as the activeingredient for antibacterial property in the fibers. Morphology of electrospun fibers wasinfluenced by solution parameters (viscosity, conductivity, surface tension) and process parameters(electric field strength, flow rate, collector type). This investigation used different types andmolecular weights of polymers (PVP K90, PVP K30, PVA MW 85,000-146,000 and PVAMW 47,000) to influence the spinnability of the polymer solution and so the morphology ofthe electrospun fibers. It was found that PVP K90 at 8-10% (w/v) in ethanol and PVA MW85,000-146,000 at 10% (w/v) in deionized water produced electrospun fibers withappropriated quality and stability. Ethanol and deionized water were used as a mixed solventto study the effect of co-solvent on fiber morphology. The results showed that increasinganother solvent in the polymer solution changed the morphology of electrospun fibers andaffected the stability of electrospun fibers. Incorporated propolis (2% w/v) and small amountof additives into PVP K90 (8% and 10% w/v) nanospun fibers gave smooth and uniformfiber morphology with diameters ranging from 0.55-0.95 μm and produced fiber mats whichwetted and dissolved rapidly in water within 10 seconds.

Keywords: electrospinning, fast dissolving fibers, propolis, polyvinyl pyrrolidone, polyvinylalcohol

1. INTRODUCTIONElectrospinning is one technique that

uses electrohydrodynamics for producingfine fibers by electrostatic forces. Fibers from

this technique have small diameters rangingfrom nanometers to micrometers. The termelectrospinning is derived from electrostatic

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470 Chiang Mai J. Sci. 2015; 42(2)

spinning [1]. There are many advantages ofthe electrospinning process such as it is asingle step and a simple technique for fiberformation. It can produce smaller diameterand higher surface area fibers when comparedwith other fiber formation techniques[1,2]. There are applications of electrospunfibers in many fields of industry. Electrospunnanofibers are used in medical fields as tissueengineering scaffolds such as cartilages, dermaltissue, bones, blood vessels, nerves, etc [3,4].Nanofibrous membranes are uesd as wounddressing and skin care masks in cosmetics.Microfibrous and nanofibrous structure ofmembranes improve the absorption ability ofwound fluid and the vapor transmission rateand transfer rate of drugs or additives willbe better [2,5,6]. For drug delivery systems,electrospun fibers have the ability toincorporate drugs inside the fibers and enabledrug delivery systems such as transdermal,implantable devices and fast dissolving drugdelivery systems.The fast dissolving dosageform is a solid dosage form that disintegratesand dissolves quickly in the oral cavity.There are many kinds of fast dissolvingdrug delivery systems such as tablets,capsules, wafers and a recent one is filmsthat are gaining much attention due to moreflexibility and comfort. Several techniquesexist to produce fast dissolving drug deliverysystems. For examples; melt extrusion,sublimation, freeze drying or directcompression have been used to preparefast dissolving dosage forms[7-9]. Theelectrospinning of suitable water solublepolymers is also an effective way forproviding fast dissolving electrospun fibersas thin films[10,11]. Fiber formation and itsstructure are the key factors to producegood properties for drugs to release fromnanofibers. Process parameters suchas applied voltage, polymer flow rate,capillary-collector distance and solution

parameters such as polymer type, polymerconcentration, solution conductivity have tobe considered [3,12].

Propolis is a resinous mixture that honeybees collect from the buds of numerous treespecies for use in defence of the hive. It usuallycontains resin; composed of flavonoids andphenolic acids (50%), waxes (30%), essentialoils (10%), pollen (5%) and various organiccompounds (5%). The antibacterial andantifungal properties of propolis are known[13,14]. There is evidence for antibacterialcapabilities of propolis in the oralcavity [15-17]. Today propolis is currentlyused in products for oral use such asmouthwashes, mouth spray or in throatlozenges. In this study, we aim to determinesuitable water polymer based nanofibers foruse as fast dissolving films with addedpropolis and other additives that can be usedin oral care products such as breath fresheneror for antibacterial treatment in the oral cavity.

2. MATERIALS AND METHODS2.1 Materials and Chemicals

Polyvinyl pyrrolidone MW 1,250,000(Kollidon® 90F, PVP K90) and polyvinylpyrrolidone MW 50,000 (Kollidon® 30, PVPK30) were provided from BASF (BASF,Germany). PVA MW 85,000-146,000 andPVA MW 47,000 (Mowiol® 6-98) weresupplied from Sigma-Aldrich (Germany).Propolis was purchased from ChiangmaiHealthy Product Co., Ltd. (Thailand).Absolute ethanol was obtained from Merck(Germany). Menthol, methyl salicylate,eucalyptus oil and thymol were purchasedfrom Union Science (Thailand).

2.2 Preparation of The Spinning SolutionsDifferent concentrations of PVP were

prepared by dissolving PVP in ethanol(or mixture of ethanol and water) and stirredwith a magnetic stirrer at ambient temperature

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Chiang Mai J. Sci. 2015; 42(2) 471

for 2 hours. PVP K90 solutions withconcentrations of 4%, 6%, 8%, 10%, 12%(w/v) and PVP K30 with concentrations of30%, 35% and 40%(w/v) were prepared.PVA was prepared by dissolving PVA indeionized water (or mixture of water andethanol) heated up to 70°C and gently stirredfor 3 hours to dissolve the solid material.PVA (MW 85,000-146,000) solutionswith concentrations of 6%, 8%, 10%(w/v)and PVA (MW 47,000) solution withconcentrations of 20%, 25% and 30%(w/v)were prepared. To study the effect of a mixedsolvent of ethanol and water on polymerbased electrospun fibers, ethanol and waterat ratios of 10:0, 8:2, 7:3, 5:5, 3:7, 2:8 and0:10 were used as solvents for the polymersin the electrospinning process. 2%(w/v)of propolis extract and other additivessuch as menthol, thymol, methyl salicylateand eucalyptus oil in small amounts(each of 0.05% w/v except eucalyptus oil at0.01% w/v) as flavoring agents wereincorporated into suitable polymer solutionsto prepare electrospun fibers for use in theoral cavity.

2.3 Electrospinning Process10 mL of the spinning solution was filled

into a 20 mL glass syringe equipped with a20 gauge stainless steel needle (inner diameter0.66 mm). The feeding rate was controlledby a syringe pump at 2 mL per hour.To maintain a steady flow of the polymersolution from the needle to the collector,a high voltage supply was used at 15 kVfor the PVP K90 solutions, 18 kV for thePVP K30 solutions and at 22 kV for thePVA solutions to create an electricallycharged jet of polymer solution with stablebehavior. A piece of aluminium foil waswrapped over the rotating collector and the

distance between the collector and the tip ofneedle fixed at 15 cm. All electrospinningprocesses were carried out under ambientconditions.

2.4 Propolis ExtractionPropolis (cooled with liquid nitrogen) was

ground before extraction. 30 g of groundpropolis was mixed with 300 mL of 70%ethanol and extracted by using an ultrasonictechnique for 30 minutes and then filtered.The filtrate was evaporated by using a rotaryevaporator under reduced pressure attemperatures below 40°C. The residue wasfreeze dried and the dry powder of propolisextract was kept in a closed container andprotected from light.

2.5 Characterizations2.5.1 Physical properties of the spinningsolutions

The electrical conductivity of thespinning solutions was measured by aconductivity Meter: Mettler-Toledo AG 8603(Switzerland). Tensiometer (Kruss® K6,Germany) was used to measure the surfacetension of the spinning solutions. Viscometer(Brookfield, DV-II, USA) was used tomeasure the viscosity of the spinningsolutions.

2.5.2 Morphology of nanospun fibersScanning electron microscopy (FIB

Quanta 200 3D) was used to investigatethe morphology of the electrospun fibers.Prior to examination, the electrospun fiberswere gold sputter-coated under argonto render them electrically conductive.The diameters of electrospun fibers weremeasured at more than 50 points fromSEM images by using Image J software andthe average calculation.

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2.5.3 Physical state and compatibility ofthe components in the nanospun fibers

Differential scanning calorimetry (DSC)analyses were obtained using a MettlerToledo851-e (Switzerland) for thermalanalysis of the electrospun fibers. X-raydiffraction analyses (XRD) were obtainedon Miniflax II X-ray diffractometer,RigaKu (Japan) in the 2θ range of 5-60°.FT-IR analysis was used to qualitativelycharacterize the functional groups of thesubstances in electrospun fibers. FT-IRspectra were collected using a ThermoNicolet 6700 Thermoscientific (USA) asKBr pellets.

2.5.4 Wetting and dissolution propertiesof electrospun fibers

Wetting time and dissolution propertiesof electrospun fibers were test follow bythe procedure from the literatures [10-11].Two layers of absorbent paper were place ina petri dish with a diameter of 10 cm andwetted with distilled water, excess water wasdrained away. The electrospun fibers wereplaced on the wet paper and observed forthe time that electrospun fibers werecompletely dissolved in water on wet paper.

3. RESULTS AND DISCUSSION3.1 Preparation of Polymer Based Electro-spun Fibers3.1.1 Effect of molecular weight of thepolymer and the concentration of spinningsolution

The molecular weight and concentrationof the polymer are the critical factorsinfluencing the morphology of theelectrospun fibers[1,3]. This part of the studywas to investigate suitable concentrations ofeach water soluble polymer for theelectrospinning process.

Different molecular weights of PVP andPVA at various concentrations were studied.

The viscosity of the polymer solutionincreased when the concentration ofpolymer solution increased. It was foundthat morphology and diameter of fibers weredependent on the polymer concentrationand the results are shown in Table 1.The sample of PVP K90 4%(w/v) showeda lot of bead formation and when theconcentration was increased to 6%(w/v),bead formation decreased with more fibers.Smooth and uniform fibers with diametersin the range of 0.43-0.64 μm were obtainedwhen the concentration of PVP K90 was8-10%(w/v). In the case of PVP K30,the concentration of PVP K30 wasincreased to 40%(w/v) to produce uniformelectrospun fibers without bead formationwith average diameter at 2.18 μm. For PVA(MW 85,000-146,000), the results showedthat the sample with 6%(w/v) concentrationproduced electrospun fibers mixed withbead formation. Bead formation decreasedwith increased polymer concentration.When the spinning concentration of PVA(MW 85,000-146,000) was increased to10%(w/v), smooth and uniform fibers thathad an average diameter around 0.18 μmwere obtained. For the low molecularweight of PVA (MW 47,000), 30%(w/v)concentration of polymer solution was thesuitable concentration to produce nanospunfibers that were free from bead formationwith average diameter at 0.19 μm. It wasconcluded that the low concentrationpolymer solutions resulted in beadformation rather than fibers. With increasedconcentration of polymer solution, smoothand uniform fibers were formed and thediameter of fibers increased also, becausethe high concentration of polymer solutionincreased the solution viscosity and the chainentanglements were sufficient to stabilizethe polymer jet along the distance to thecollector [18,19]. Low molecular weight

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polymers(PVP K30 and PVA MW 47,000)had to use higher concentrations ofpolymer solution when compared withhigh molecular weight polymers (PVPK90 and PVA MW 85,000-146,000) toproduce good morphology of electrospun

fibers. Thus, we chose PVP K90 and PVA(MW 85,000-146,000) for further studyand the optimal concentration of polymersolution for further electrospinningprocesses was selected as 10%(w/v) forboth.

3.1.2 Effect of mixed solvent on polymerbased electrospun fibers

A suitable solvent is one of the importantfactors that influence the morphology ofnanospun fibers[20-22]. Mixed solvents ofethanol and water in various ratios were usedin this study. Small amounts of water weremixed with ethanol to dissolve PVP K90with a constant concentration of PVP K90of 10%(w/v). SEM photographs of PVPK90 nanospun fibers produced at differentratios of ethanol: water (10:0, 8:2) are

presented in Figure 1(a) and 1(b). The resultsshowed that, addition of water (ethanol:water; 8:2) decreased the diameter of thefibers and the fibers tended to be unstable.Nanospun fibers with some water in thesolvent that attatched on the collectordissolved in ambient condition after theelectrospinning process finished. For decreasedratio of ethanol: water (7:3),a droplet ofpolymer solution collected on the aluminumfoil instead of nanospun fibers. Theconcentration of PVP K90 was increased

Table 1. Experimental data of polymer solutions for electrospinning process and fiber obtained.

Type of polymers

PVP K904%6%8%10%

PVP K3030%35%40%PVA

(MW 85,000- 146,000)6%8%10%PVA

(MW 47,000)20%25%30%

Solvents

EthanolEthanolEthanolEthanol

EthanolEthanolEthanol

WaterWaterWater

WaterWaterWater

Formation

Beads ++Beads +

Uniform fibersUniform fibers

Beads ++Beads +

Uniform fibers

Beads ++Beads +

Uniform fibers

Beads ++Beads +

Uniform fibers

Diameter of fibers (μm)

--

0.43 ± 0.090.64 ± 0.16

--

2.18 ± 0.35

--

0.18 ± 0.03

--

0.19 ± 0.05

+, ++ : Indicates amount of beads in electrospun fibers

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from 10%(w/v) to 12%(w/v)for the sameratio of mixing solution of ethanol and waterused as solvent. Figure 1(c)-1(e) shows12%(w/v) PVP K90 electrospun fibers fromthe polymer solution in ethanol: water atratios of 10:0, 8:2 and 7:3 respectively.The results indicated that the increasedconcentration of PVP K90 of 12%(w/v)increased the diameter of the fibers, withmore stable fiber formation in ambientconditions. Larger amounts of water in thissystem (ethanol: water; 7:3) resulted in beadformation. For PVA (MW 85,000-146,000),which was soluble in water, small amountsof ethanol were mixed with water for thesolvent system. Water:ethanol at variousratios 10:0, 8:2, 7:3 and 5:5 were used todissolve 10%(w/v) PVA(MW 85,000-146,000) and the SEM images of the resultednanofibers are shown in Figure 2(a)-2(d).SEM photographs indicated that addingethanol into the system influenced themorphology of the fibers. The diameter offibers increased with increased ethanol in themixed solvent. At the ratio of ethanol: water;5:5, nonuniform and very large diameterfibers were formed. Physical properties ofthe polymer solutions; conductivity, surfacetension, viscosity and measured diameters ofthe electrospun fibers are shown in Table 2.It can be concluded that increasing waterin ethanol as the mixed solvent for PVPK90 increased the conductivity and surfacetension but decreased the viscosity ofthe electrospinning solvent, which resultedin thinner fiber formation. High amountsof water introduced bead formation(Figure 1(b) and 1(e)). When the viscosity ofthe electrospinning decreased perhaps thepolymer chain entanglement were low sobeads were formed instead of fibers.Water has a low evaporation rate comparedwith ethanol, so added water decreasedevaporation rate of the electrospinning

solvent. The solvent had not evaporatedcompletely before the polymer jets reachedthe collector and created unstable fibers thatdissolved rapidly in ambient condition afterthe electrospinning process. For PVA (MW85,000-146,000), increased ethanol in thesystem decreased conductivity and surfacetension but increased viscosity significantly.High viscosity of electrospinning solutionhad a greater influence on morphology ofthe electrospun fibers. At higher viscosity,it is harder to stretch the polymer jet to createfine fibers, thus the fibers had large diametersand formed beads(Figure 2(c) and 2(d)).

For a study of the dissolution propertiesof electrospun fibers in water, PVA (MW85,000-146,000) fibers dissolved within30 seconds whereas PVP K90 fibersdissolved within 10 seconds. Although PVA(MW 85,000-146,000) can produced fiberswith good morphology, the dissolution timeof fibers was slower than for PVP K90fibers. This result showed that PVP K90has strong potential for use as a polymerbase in the electrospinning process toproduce fast dissolving dosage forms or

Figure 1. SEM images of PVP K90electrospun fibers at a concentration of10%(w/v) in solvents: (a) pure ethanol (b)ethanol:water 8:2 and at a concentrationof 12%(w/v) PVP K90 in solvents:(c) pureethanol (d) ethanol:water 8:2 and(e)ethanol:water 7:3.

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Table 2. Physical properties of PVP K90 and PVA (MW 85,000-146,000) polymer solutionsin different mixed solvents and average electrospun fiber diameters.

Type of solutions

10% (w/v) PVP K90in ethanol10% (w/v) PVP K90in ethanol:water (8:2)12% (w/v) PVP K90in ethanol12% (w/v) PVP K90in ethanol:water (8:2)12% (w/v) PVP K90in ethanol:water (7:3)10% (w/v) PVAin water10% (w/v) PVAin water:ethanol (8:2)10% (w/v) PVAin water:ethanol (7:3)10% (w/v) PVAin water:ethanol (5:5)

Conductivity(ms/cm)

11.40

20.06

11.86

22.00

26.60

1013.33

581.76

453.00

357.67

Surface tension(mN/m)

25.45

28.22

26.06

28.80

29.81

47.52

45.72

42.30

34.74

Viscosity(cP)

850.00

< 800.00

1163.33

1143.33

1146.67

1613.33

2056.67

3283.33

4290.00

Averagediameter offibers (μm)0.64 ± 0.16

0.16 ± 0.08

0.68 ± 0.12

0.46 ± 0.09

beads

0.18 ± 0.03

0.35 ± 0.11 + beads

0.35 ± 0.09 + bead

3.65 ± 0.92 + beads

improve the dissolution of the drugs as hasalso been reported in previous studies [11,23].Thus, the most suitable system for theelectrospinning process with added propoliswas PVP K90 polymer in pure ethanol assolvent.

3.2 Incorporation of Propolis andAdditives into Electrospun Fibers

Propolis extract can be formulated at1-10% (w/v) in oral care products.2% (w/v) propolis in PVP K90 polymersolution was prepared for electrospinningprocess. SEM photographs showedthat 2% (w/v) propolis incorporatedwith/without additives into 10%(w/v)PVP K90 solution produced smooth anduniform electrospun fibers and tended toincrease the diameter of fibers when

Figure 2. SEM images of PVA (MW85,000-146,000) at a concentration of10%(w/v) in solvents: (a) pure water, (b)water:ethanol 8:2, (c) water:ethanol 7:3, (d)water:ethanol 5:5.

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compared with polymer only electrospunfibers. The average fiber diameters were0.93 μm and 0.89 μm for electrospun fibersof 10% (w/v) PVP K90 with 2% (w/v)propolis and electrospun fibers of 10%(w/v) PVP K90 with 2% (w/v) propoliscombined with additives (Figure 3(a) and3(b)) respectively. As the results thatshowed before, smooth and uniform fiberswere obtained when the concentration ofPVP K90 was 8-10%. 8% (w/v) PVP K90was also studied to compare with 10%(w/v) PVP K90. Figure 3(c) and 3(d)shows smooth and uniform fibers from8% (w/v) PVP K90 with 2% (w/v)propolis and 8% (w/v) PVP K90 with2% (w/v) propolis and additives, withaverage diameter 0.56 μm and 0.61 μmrespectively. It was found that all of thePVP K90 electrospun fibers with propolisand additives dissolved rapidly within 10seconds.

3.3 Physical State and Compatibility ofThe Component in The NanospunFibers

FTIR spectra are shown in Figure 4.The characteristic peaks of PVP K90 at2594 cm-1 (C-H stretching), 1649.44 cm-1

(C=O stretching), 1461.31 cm-1(C-H beadingof CH2) and 1285.68 cm-1 (C-N stretching)are shown in Figure 4(a). Due to thehydrophilic nature of PVP, a broadband was observed (O-H stretch) atabout 3500 cm-1[24,25]. The spectrumof propolis shows characteristic peaks at1687.44 cm-1, 1625.72 cm-1, 1598.21 cm-1,1375.94 cm-1, 1257.64 cm-1, 1160.01 cm-1

and 1058.88 cm-1 in Figure 4(b) whichcorrespond to functional groups offlavonoids, lipids and alcohol groups inpropolis extract [26,27]. In Figure 4(c) and4(d) characteristic peaks of electrospunfibers of PVP K90 with propolis with andwithout additives are shown. The mainpeaks of PVP K90 and propolis can also beobserved in these spectra. These resultsindicated that propolis and PVP K90with additives used in this study hadgood compatibility.

Figure 3. SEM images of 10% (w/v) PVPK90 elecrospun fibers with (a) 2% (w/v)propolis, (b) 2% (w/v) propolis withadditives and 8% (w/v) PVP K90elecrospun fibers with (c) 2% (w/v)propolis, (d) 2% (w/v) propolis withadditives.

Figure 4. FTIR spectra: (a) propolisextract, (b) PVP K90, (C) PVP K90electrospun fibers with 2%(w/v)propolisand (d) PVP K90 electrospun fibers with2%(w/v)propolis with additives.

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DSC thermograms of electrospunfibers of PVP K90 with propolis andadditives are shown in Figure 5(c) and 5(d)compared with raw material of propolisand PVP K90 in Figure 5(a) and 5(b),respectively. Raw material of PVP K90showed broad endothermic curve.Whereas, electrospun fibers of PVP K90with propolis, endothermic curvebecame obtuse and the peak shiftedtoward the low temperature and thepropolis lost its shape and distinctiveappearance. These results showed that thecrystalline microstructure of electrospunfibers did not form.This was because themajority of the chains are in the non-crystalline state due to the rapidsolidification process of stretched chainsduring electrospinning process[28].

additives (Figure 6(c) and6(d)), indicatingthat all of the materials in the nanofiberswere in an amorphous state and theelectrospinning process did not lead tothe development of the crystallinemicrostructure of electrospun fibers.The results from XRD were supported byDSC analysis.

Figure 5. DSC thermograms: (a) propolisextract, (b) PVP K90, (C) PVP K90electrospun fibers with 2%(w/v) propolisand (d) PVP K90 electrospun fibers with2%(w/v) propolis with additives.

The XRD patterns of propolis, PVPK90 and electrospun fibers of PVP K90with propolis and additives are comparedin Figure 6. There are no peak of crystallinein the XRD patterns of the electrospunfibers of PVP K90 with propolis and

Figure 6. XRD patterns: (a) propolisextract, (b) PVP K90, (C) PVP K90electrospun fibers with 2%(w/v) propolisand (d) PVP K90 electrospun fibers with2%(w/v) propolis with additives.

4. CONCLUSIONIn this study, orally fast dissolving

fibers were developed from PVP and PVAas the filament-forming materials byelectrospinning technique. All of polymers(PVP K90, PVP K30, PVA MW 85,000-146,000 and PVA MW 47,000) can producesmooth nanospun fibers at differentconcentrations. Using ethanol anddeionized water as mixed solvent influencedthe morphology and stability of the fiberswhen compared with pure solvent. Theresults from testing of dissolutionproperties between 10% (w/v) PVP K90and 10% (w/v) PVA (MW 85,000-146,000)electrospun fibers showed 10% (w/v) PVPK90 electrospun fibers had fasterdissolution rate than 10% (w/v) PVA(MW 85,000-146,000)electrospun fibers.PVP K90 and pure ethanol was the mostsuitable polymer and solvent for the

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[3] Sill S.C. and Von Recum H.A.Electrospinning: Application in drugdelivery and tissue engineering,Biomaterials, 2008; 29: 1089-2006.DOI 10.1016/j.biomaterials.2008.01.011.

[4] Bhattarai S.R., Bhattarai N., Yi H.K.,Hwang P.H., Cha D.I. and Rim H.Y.,Novel biodegradable electrospunmembrane: Scaffold for tissueengineering, Biomaterials, 2004; 25:2595-2602. DOI 10.1016/j.biomaterials.2003. 09.043.

[5] Taepaiboon P., Rungsardthong U.and Supaphol P., Vitamin-loadedelectrospun cellulose acetate nanofibermats as transdermal and dermaltherapeutic agents of vitamin A acidand vitamin E, Eur. J. Pharm.Biopharm., 2007; 67(2): 387-397. DOI10.1016/j.ejpb. 2007.03.018.

[6] Fathi-Azarbayjani A., Qun L., ChanY.W. and Chan S.Y., Novel vitaminand gold-loaded nanofiber facial maskfor topical delivery, AAPS PharmSciTech,2010; 11(3): 1164-1170. DOI 10.1208/s12249-010-9475-z.

[7] Siddiqui N., Gard G. and SharmaP.K., A short reviw on A novelapproach in oral fast dissolving drugdelivery system and their patents, Adv.Biol. Res., 2011; 5(6): 291-303.

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electrospinning process to produce orallyfast dissolving fibers and also ethanol wasa good solvent to dissolve propolis and allof the solid material in these formulations.8% and 10% (w/v) PVP K90 electrospunfibers containing 2% (w/v) propolis withadditives were successfully prepared by theelectrospinning technique. SEMphotographs showed good morphologyand uniform fibers with diameter ranging0.55-0.95 μm. XRD patterns and DSCresults showed the amorphous structure ofthe nanofibers. FTIR spectra suggested thatPVP K90 and propolis have goodcompatibility. The electrospun fibers wereable to rapidly dissolve on wet paperwithin 10 second. These results show thepotential to be developed as orally fastdissolving fibers of these electrospun fiberswith propolis for use in the oral cavity.Antibacterial activity of electrospun fiberswith propolis will be tested in furtherstudy.

ACKNOWLEDGEMENTSThe authors would like to express their

sincere gratitude to the Graduate School,Faculty of Pharmacy and Faculty ofScience, Chiang Mai University, Thailandfor their support. Financial support fromthe National Research University Projectunder Thailand’s Office of the HigherEducation Commission (OHEC) isgratefully acknowledged. The authorswould to thank Dr. Denis RussellSweatman for checking the manuscript.

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