International Journal of Pharmaceutics 475 (2014) 351–363

Influence of surface modification on wettability and surface energycharacteristics of pharmaceutical excipient powders

Vikram Karde, Chinmay Ghoroi *Chemical Engineering, Indian Institute of Technology Gandhinagar, VGEC Campus, Chandkheda, Ahmedabad, India

A R T I C L E I N F O

Article history:Received 5 June 2014Received in revised form 29 August 2014Accepted 3 September 2014Available online 6 September 2014

Keywords:Contact angleSurface wettabilitySurface energySpreading co-efficientWork of adhesion

A B S T R A C T

Influence of surface modification on wettability and surface energy characteristics of three micron sizepharmaceutical excipient powders was studied using hydrophilic and hydrophobic grades of nano-silica.The wetting behavior assessed from contact angle measurements using sessile drop and liquidpenetration (Washburn) methods revealed that both techniques showed similar wettability character-istics for all powders depending on the hydrophilic or hydrophobic nature of nano-coating achieved. Thepolar (gs

p) and dispersive (gsd) components of surface energies determined using extended Fowke’s

equation with contact angle data from sessile drop method and inverse gas chromatography (IGC) atinfinite dilution suggested a general trend of decrease in gs

d for all the surface modified powders due topassivation of most active sites on the surface. However, depending on the nature of the functionalgroups present in nano-silica, gs

p was found to be either higher or lower for hydrophilic or hydrophobiccoating respectively. Results show that wettability increases with increasing gs

p. Both the techniques ofsurface energy determination provided comparable and similar trends in gs

p and gsd components of

surface energies for all excipients. The study also successfully demonstrated that surface wettability andenergetics of powders can be modified by varying the level of surface coating.

ã 2014 Elsevier B.V. All rights reserved.

Contents lists available at ScienceDirect

International Journal of Pharmaceutics

journal homepage: www.elsev ier .com/locate / i jpharm

1. Introduction

Surface characterization of the solid provides better under-standing of their behavior in different processes. Surface wettabil-ity and surface energetics of powders are most critical properties tobe taken into consideration during formulation and developmentof a solid and liquid dosage forms in pharmaceutical industry.Changes in wettability characteristics of powders can havesignificant effect on pharmaceutical processes such as granulation,disintegration, dissolution, dispersibility etc. Similarly, surfaceenergy of powder plays an important role in determining thephysicochemical properties such as wettability, adhesion, flow-ability, packing etc. Both surface wettability and energetics areprone to physical or chemical changes occurring on the solidsurface. While wettability can be predominantly affected by thechemical nature of surfaces, the surface energy can be affected byvarious factors like powder processing or handling conditions,

* Corresponding author. Tel.: +91 793 245 9897; fax: +91 792 397 2583.E-mail addresses: chinmayg@iitgn.ac.in, chinmayghoroi@gmail.com (C. Ghoroi).

http://dx.doi.org/10.1016/j.ijpharm.2014.09.0020378-5173/ã 2014 Elsevier B.V. All rights reserved.

environmental conditions, particle size (Buckton et al., 1988; Hanet al., 2013) etc.

In pharmaceutical industry, the conventional method employedfor surface modification of solids includes applying solvent basedfunctional polymer coating. Surface modification through drycoating using nano-particle is comparatively recent technique(nano-coating) where nano-particles are employed as ‘guest’particle for coating the surface of bigger size ‘host’ particle (Pfefferet al., 2001). It involves mechanical force where nano-particles arefirst de-agglomerated and then dispersed on to the surface of hostparticle. Dry particle coating being a solventless technique offerslarge number of advantages over the conventional solvent basedtechniques for property modification of powders. Owing to itssimplicity and cost effectiveness, dry coating technique isbecoming popular among the scientific community for modifyingparticle surface properties. Various researchers have employedthis technique of particle surface modification for differentapplications which include improving powder flow (Jallo et al.,2012), fluidization (Ghoroi et al., 2013a), dispersion (Ghoroiet al., 2013b), aerosolization (Zhou et al., 2010), dissolution (Hanet al., 2011, 2012; Tay et al., 2012) and also for modifying wettabilitycharacteristics (Lefebvre et al., 2011; Mujumdar et al., 2004;

352 V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363

Ramlakhan et al., 2000) as well as surface energetics of powders(Gamble et al., 2013; Han et al., 2013).

For the assessment of wettability of solid surface, contact angledetermination is one of the most commonly used methods. It canbe determined using different approaches such as sessile droptechnique (Luner et al., 1996), liquid penetration method(Washburn method) (Washburn, 1921), Wilhelmy method (Pepinet al., 1997), thin layer wicking method (Van Oss et al., 1992) etc.However, the two former methods are most popular. Lefebvre et al.(2011) studied the effect of surface modification on wettability anddispersibility of talc powders which were dry coated withhydrophobic silica particles in Cyclomix high shear mixer. Theyused sessile drop method for wettability measurement and foundthat concentration of nano-particle and processing time both affectthe wettability. They observed that work of adhesion calculatedfrom contact angle influenced the dispersion rate of talc powder inwater. Similarly, Ouabbas et al. (2009) used Cyclomix high shearmixer for surface modification of silica gel and corn starch particlesby dry coating with different percent w/w of magnesium stearateand different grades (hydrophobic and hydrophilic) of fumed silicarespectively. The wettability was studied by the sessile dropmethod and dynamic vapor sorption (DVS) measurements. Theresults indicated that dry coating of silica gel powder byhydrophobic magnesium stearate resulted in improvement of itshydrophobic properties. The moisture adsorption–desorptionisotherms of uncoated and coated particles obtained from dynamicvapor sorption analyzer also suggested altered moisture adsorp-tion and desorption characteristics of powders (Ouabbas et al.,2009).

Similarly, for assessment of surface energetics of solids, thereare various techniques available such as techniques based onwettability determination like contact angle determination usingsessile drop method (Luner et al., 1996; Puri et al., 2010) or liquidpenetration method (Siebold et al., 1997), techniques based on gasadsorption phenomenon like inverse gas chromatography (IGC)(Das et al., 2011; Newell et al., 2001) and based on thermodynamicprinciples like microcalorimetry (Buckton and Beezer,1988). Whilecontact angle method has been widely used (mostly compresseddisc technique) to evaluate the surface characteristics of solids(James et al., 2008; Luner et al., 1996), in recent years IGC has beenconsidered as a more accurate and sensitive alternative for surfaceenergy determination (Buckton and Gill, 2007).

Different studies comparing the surface energy determined fromthese two methods suggested a great degree of agreement fordispersive component of the surface energy (Dove et al.,1996; Henget al., 2006; Planinsek et al., 2001). Dove et al. (1996) studied thewettability and surface energetics of theophylline and caffeinepowders from contact angle and inverse gas chromatography (IGC)methods respectively. They found that dispersive component ofsurface energies obtained from IGC was almost identical to thatfrom contact angle method. Dispersive surface energies of pharma-ceutical powders were also compared from these two differentapproaches by Planinsek et al. (2001). They also suggested that agood correlation of results for these methods can be obtainedprovided diiodomethane or bromonaphthalene is used to determinethe non-polar components in contact angle studies.

In all these studies, the dispersive component of surface energywas found to be comparable from both the techniques. However,analysis based on polar component of surface energy has still notbeen discussed in literature. Thus, a direct comparison of polarcomponent of surface energy, which otherwise has a greatsignificance for complete characterization of solid surface ener-getics is missing in the literature. Although numerous studies havereported the comparative accounts for wettability property fromdifferent methods, a comprehensive study of wettability andsurface energetic properties together from different methods and

their interrelation is lacking in open literature. This work isplanned to compare wettability and surface energy of powdersseparately from two different techniques. A comprehensiveanalysis of these results based on the morphological aspects andchemical nature of particle surfaces is also planned.

With this aim, the influence of surface modification onwettability and surface energetics of three commonly usedexcipient powders viz. Avicel PH 105, lactochem fine powderand corn starch was assessed before and after their surfacemodification using hydrophilic and hydrophobic colloidal silicanano-particles. Also, the effect of surface morphology on quality ofthe surface modification for these fine powders was studied. Thewettability of coated and uncoated powders was evaluatedthrough contact angle measurement using sessile drop and liquidpenetration methods. The wettability characteristics were alsoexplained in terms of work of adhesion and spreading coefficient.Surface energy of these powders was determined using contactangle data from sessile drop method and from IGC at infinitedilution. Results for both wettability and surface energydetermined from different methods were then compared andcorrelated. The extent of surface modification and its effect onwettability and surface energetics of the powder was also studiedusing corn starch powder with different percentage of hydropho-bic nano-silica coating.

2. Experimental

2.1. Materials

Microcrystalline cellulose (Avicel PH105, FMC Biopolymers),lactose monohydrate (Lactochem fine powder, Domo Friesland)and corn starch (Suru Pharma, India) were used as ‘host’ powdersfor nano-coating. Hydrophilic fumed silica grade (Aerosil 200P)and hydrophobic fumed silica grade (Aerosil R972 Pharma) havingmean particle size of around 12 nm and 16 nm respectively wereobtained as a gift sample from Evonik/Degussa Industries, USA andwere selected as ‘guest’ particle for nano-coating. De-ionizedwater (Milipore, USA) and glycerol (Merck, USA) were used as polartest liquids; and diiodomethane (National Chemicals, India) andn-hexane (Merck, USA) were used as non-polar probe for contactangle determination studies. For inverse gas chromatographyexperiments Decane (Spectrochem, India), Nonane (Merck, USA),Octane (Spectrochem, India) and Heptane (RANKEM, India) wereused as non-polar alkane probes whereas dichloromethane (Finar,India) and ethyl acetate (Finar, India) were used as polar probes.

2.2. Dry coating process

Dry coating of excipient powders was performed in a Co-mill(Prism Pharma Machinery, India) using hydrophilic and hydro-phobic grades of nano-silica following a method described in theliterature (Mullarney et al., 2011). Co-mill provides intensivemixing between the host (excipient) and guest (nano-silica)particles with the help of impellers resulting in coating of the hostsurfaces with guest particles. Prior to coating experiment, theexcipient powder and nano-silica were co-sifted through 30 meshBSS sieve and pre-mixed in V-blender at 15 �1 rpm for 10 min. Theblend was then passed through Co-mill operating at 1800 � 1 rpmto achieve the required coating. Based on the bulk propertycharacterization previously performed in the lab, about 0.5% w/wlevel of Aerosil R972 (hydrophobic) and 1.0% w/w level of Aerosil200P (hydrophilic) were used for coating all three excipients.Further, to study the effect of percentage of surface area coverageon wettability and surface energy, only corn starch was coated with0.25%, 0.5% and 1% w/w of Aerosil R972. All the experiments wereperformed at room conditions of 40 � 5% RH and 25 � 2 �C.

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 353

2.3. Particle size and morphology

To investigate any change on the particle size of the coatedexcipients due to the co-milling process employed for dry coatingpurpose, laser diffraction particle size analyzer (Cilas, Model 1190)was used for the particle size determination of uncoated and drycoated excipient powders using dry analysis mode (air dispersionmode). The mean and median diameters (d50) of powder sampleswere determined at an air dispersion pressure of 1 bar.

The surface morphology for uncoated and nano-coated excipi-ent samples were examined using field emission scanning electronmicroscope (FESEM) (JEOL JSM 7600 F, USA). The FESEM analysiswas done with working distance (WD) of 4.5–6.0 mm and a voltageof 1.5–2.0 kV.

All coated and uncoated powder samples were then studied fortheir wettability and surface energetics.

2.4. Wettability determination studies

Wettability determination was carried out with two methodsviz. sessile drop method using water, glycerol as polar liquids anddiiodomethane as non-polar liquid; and liquid penetration method(Washburn method) using water as polar and n-hexane as non-polar liquid.

2.4.1. Wettability studies using sessile drop methodThe contact angle for the excipient samples were determined

directly using sessile drop goniometric method. For these experi-ments, flat surfaces of the excipient powders were formed bypreparing discs (pellets) on IR Press. About 200 mg of excipientpowders were taken and compressed at 2 t pressure to get pellet of13 mm diameter. All the prepared compacts were stored in air tightcontainers prior to the experiments.

As surface roughness plays an important role in wettabilitystudies using contact angle measurements (Ryan and Poduska,2008), AFM (Nanoscope, Bruker) studies were carried out so as todetermine surface roughness of the excipient pellets. A scan size of5 m � 5 m was used to obtain the AFM images for surface roughnessdetermination studies. AFM images obtained were then analyzedusing nanoscope software to report the average roughness (Ra) andrms roughness (Rrms) values from three different regions of thecompacts.

Contact angles measurement was performed by goniometricmethod using polar liquids water and glycerol; and non-polarliquid diiodomethane. The details of surface tension property oftest liquids are given in the Table 1. The contact angles weremeasured using Theta Optical Tensiometer (KSV Instruments)consisting of a sample stage, light source, lens and image capturecamera. A small drop of liquid was placed on the surface of thepellet using a syringe and the drop images were captured usinghigh speed camera at 0.02 s intervals of time. The drop volume ofapproximately 2 ml for water, 6 ml for glycerol and 0.5 ml fordiiodomethane were used for the measurements. Mean contactangle was determined directly from the captured images bymeasuring the angle formed between the solid and the tangent tothe drop surface with the help of Attension Theta software.

Table 1Surface tension parameters for test liquids (Planinsek et al., 2001).

Dispersive component,g l

dPolar component,g l

pTotal,g l

t

(mN/m) (mN/m) (mN/m)

Water 21.8 51 72.8Glycerol 34 30 64Di-iodomethane 50.8 0 50.8

Measurements using the above mentioned liquids were repeatedon different surfaces of the same material which were thenaveraged. All the measurements were performed at the roomtemperature of 25 � 2 �C and a relative humidity of 40 � 5%.

The affinity of liquid for a solid surface can also be quantifiedusing work of adhesion (Zisman, 1964) which represent the workrequired to extract a drop of the test liquid from a solid surface.Work of adhesion (Wa) between a liquid and solid (compacts) wasdetermined from the surface energy value of liquid (g l

t) andcontact angle (u) obtained by goniometric method using Eq. (1).

Wa ¼ g ltð1 þ cos uÞ (1)

The greater the work of adhesion; more is the interactionbetween liquid and solid surface that is, surface is more wetting innature.

2.4.2. Wettability studies using liquid penetration methodIn addition to the static contact angle measurement using

sessile drop method, the advancing contact angle as well as liquidpenetration rate was determined using an experimental setup tomeasure the mass gain of liquid in powder bed as a function oftime. The apparatus and the experimental procedure used wassimilar to that described by Thakker et al. (2013). The assemblyconsisted of a sample holder in the form of a cylindrical metallictube, perforated at the bottom and hanged to a microbalance hookfrom the top. A Petri dish containing the test liquid was placed justbelow the perforated end of the holder on a mechanical platform. Afilter paper was placed at the perforated end of the sample holderto support the powder sample. About 2 g of sample was filled andpacked uniformly using an automatic tapper (Veego InstrumentsCorporation, TAP/MATIC-II model, India). The test liquid was thengradually brought into contact with perforated end of the tubewith the help of a manual jack and the mass gain vs. time wasrecorded. A combination of test liquid (deionized water) and astandard completely wetting liquid (n-hexane) was used for thewettability determination experiments. All the experiments wereperformed in triplicates at 25 � 2 �C and between each experi-mental run the sample holder was cleaned and dried thoroughly.The contact angles for different liquid and powder systems weredetermined using modified Washburn equation which providesrelationship between liquid penetration rate and contact angle (u)as given below

T ¼ hCr2g lcos u

� �M2 (2)

where T is time of contact; M, h, r and g l are mass gain, viscosity,density and surface tension of liquid respectively and C is materialconstant which depends on powder bed porosity (e), equivalentpore radius (rc) and powder packing radius (R) as given by Eq. (3),

C ¼ rce2ðpR2Þ22

(3)

For the determination of advancing contact angle frommodified Washburn method, only the linear part of mass squarevs. time curve was used for calculations. Also, considering the flowinstabilities reported in literature at the initial wetting stage(Siebold et al., 2000, 1997), the time points only after 10 s from theinitial contact were used for calculation purpose. In general, higherslope of mass square vs. time curve indicates lower contact anglesimplying higher wettability. The penetration rate (dM/dt) was alsocalculated for each powder sample.

As material constant (C) depends on powder packing, thepoured and tapped density of the powder was determined usingconventional graduated cylinder method and automatic tappeddensity apparatus. These results correlated with the materialconstant values (C). The powder sample was gently filled in a

354 V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363

100 ml glass cylinder while keeping the cylinder in a slightlyinclined position so as to avoid the compaction of the powderduring free fall. The poured volume and mass of powder werenoted. The tap density of powder samples were determined using atap density test apparatus (Veego Instruments Corporation, TAP/MATIC-II model, India) employing USP type I test in which thecylinder is raised by a height of 14 � 2 mm and then allowed todrop under its own weight. The cylinder was tapped at a nominalrate of 300 taps per minute for a minimum of 1250 taps (500 initialtaps followed by final 750 taps). The tapping was continued till atapped volume difference of less than 2% was obtained between2 consecutive tapping sequences.

2.5. Surface energy determination studies

Surface energy of excipient powders were calculated using thecontact angle readings obtained from the goniometric method(sessile drop method) as well as from IGC at infinite dilution. Thesemethods are described below.

2.5.1. Surface energy determination from contact angle approachOwens–Wendt–Kaelble model also termed as extended

Fowke’s model based on the Young–Dupree equation was usedfor the surface free energy calculations of solid under study (Owensand Wendt, 1969). This two liquid approach for solid surfaceenergy determination utilizes the relationship between contactangle and dispersive (gd) and polar (gp) components of liquid andsolid surface energies as shown in Eq. (4).

g ltð1 þ cosuÞ ¼ 2ð

ffiffiffiffiffiffiffiffiffiffiffiffigpl g

ps

qþ

ffiffiffiffiffiffiffiffiffiffiffiffigdl g

ds

q(4)

where g lt, g l

d and g lp are the total, dispersive and polar surface

energies of liquid whereas gsd and gs

p are the dispersive and polarcomponents of solid surface energy respectively. The dispersive(gs

d) component of solid surface energy can be determined using anon-polar liquid so that the above equation can be modified to theequation given below

gds ¼ gd

l ð1 þ cos uÞ24

(5)

Putting the value of gsd calculated from Eq. (5), Eq. (4) provides

the value for gsp. Finally, the total surface energy (gs

t) of solidwhich is the sum of dispersive (gs

d) and polar (gsp) components

was calculated.Surface energy studies from contact angle approach can also be

used to extract some additional information related to thewettability characteristics of a solid surface with the help of athermodynamically determined co-efficient called as spreadingco-efficient. Spreading co-efficient (Sl/s) is an index of spreading ofa liquid over a solid surface and it can be determined from theirrespective dispersive (gd), polar (gp) and total (gt) surface energyvalues using Eq. (6) (Rowe, 1989). Increase in spreading coefficient

Table 2Mean and median diameters of uncoated and nano-coated powders.

Excipient (host material) Guest particle coating

Corn starch –

Corn starch Aerosil 200P

Corn starch Aerosil R972

Lactochem fine –

Lactochem fine Aerosil 200P

Lactochem fine Aerosil R972

Avicel PH 105 –

Avicel PH 105 Aerosil 200P

Avicel PH 105 Aerosil R972

of a liquid on a solid indicates increase in wettability of solids.

Sl=s ¼2g l

tgs

dg ld

gsd þ g l

d

� �þ gs

pg lp

gsp þ g l

p

� �� �(6)

2.5.2. Surface energy determination from IGC methodAdditionally, surface energy determination experiments were

carried out using an IGC surface energy analyzer (SurfaceMeasurement Systems, London, UK). The uncoated and coatedpowders were carefully packed into individual pre-silanized glasscolumns (300 mm length and 3 mm I.D.) and plugged withsilanized glass wool (Sigma–Aldrich, UK) at both the ends ofcolumn. Proper sample packing in the column was ensured withthe help of jolting voltameter (Surface Measurement Systems,London, UK) which provides mechanical tapping to the column soas to remove the voids in packed sample bed. Individual samplecolumns were then separately mounted into column oven with therequired column fittings. The surface energies of uncoated andsurface modified powders were determined at 0% RH and 30 �Ccolumn conditions. Each column was allowed to undergo aconditioning cycle at the set test conditions for a period of 1 hprior to the actual analysis. The surface energy analyses of thesamples were carried out at an infinite dilution (fixed probecoverage of 3%) of the non-polar and polar probes. Helium wasused as a carrier gas with a flow rate of 10 ml/min and methane wasused as a reference gas for the injections. The surface energydetermination experiments were carried out on two columns foreach sample in duplicate runs.

2.6. Wettability and surface energy as a function of nano-coating

Finally, in order to check the effect of varying level of nano-coating on wettability and surface energetics, corn starch wascoated with 0.25% w/w, 0.5% w/w and 1% w/w of nano-silica usingdry coating method. The percent surface area coverage wasdetermined experimentally from image processing of FESEMimages of coated particles using ImageJ 1.47 software andcorrelated with the wettability and surface energy characteristicsof the powder samples.

3. Results and discussion

3.1. Particle size analysis and surface morphology of powders

The mean and median particle size of uncoated and nano-silicacoated excipients are presented in Table 2. Both the uncoated andcoated excipient powders showed almost similar particle size.Therefore, it can be implied that intensive mixing and impactionforces applied during the coating process in the mixing zone of thecone mill did not reduce the particle size of the powders.

d50(mm) Mean(mm)

17.49 � 0.29 21.7 � 0.6318.18 � 0.38 22.11 � 0.6418.32 � 0.18 22.55 � 0.4732.3 � 0.42 38.92 � 0.42

31.43 � 0.36 38.32 � 0.1532.45 � 1.04 39.33 � 0.2718.5 � 0.37 21.38 � 0.42

17.57 � 0.25 20.91 � 0.2818.24 � 0.04 21.06 � 0.10

Fig. 1. FESEM images of uncoated powders (a) corn starch, (d) lactochem fine (g) Avicel PH105; Aerosil 200P coated powders (b) corn starch, (e) lactochem fine, (h) AvicelPH105; and Aerosil R972 coated powders, (c) corn starch, (f) lactochem fine, (i) Avicel PH105.

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 355

Table 3Surface roughness of excipient pellets.

Sample Ra (nm) Rrms(nm)

Starch uncoated 20.80 � 4.23 28.10 � 4.44Starch 200P 32.10 � 3.65 40.08 � 5.90Starch R972 28.70 � 5.94 36.80 � 7.04Lactochem fine uncoated 35.95 � 3.2 48.20 � 5.43Lactochem fine 200P 39.47 � 5.98 54.3 � 7.71Lactochem fine R972 28.90 � 3.84 41.40 � 5.4Avicel PH105 Uncoated 29.45 � 3.04 37.25 � 3.89Avicel PH105 200P 20.75 � 2.48 27.60 � 4.40Avicel PH105 R972 24.00 � 2.14 43.65 � 8.39

Ra:average roughness; Rrms:root mean square roughness.

356 V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363

FESEM analysis of uncoated excipient powders revealed thatcorn starch particles have nearly spherical shape with smoothsurface appearance (Fig. 1a). The lactochem particles wereslightly cylindrical in shape with relatively smooth surfacecontaining some associated fines (Fig. 1d). On the other hand,Avicel PH105 particles consisted of highly irregular shapedparticles with rough surface (Fig. 1g). FESEM images of drycoated particle shows that the corn starch particles were moreefficiently and uniformly coated (Fig. 1b and c) followed bylactochem particles (Fig. 1e and f) and least coating was achievedwith Avicel PH105 particles (Fig. 1h and i). These observationswere further confirmed from the surface energy studies,discussed in the later sections. Thus, it can be said that theextent of surface coating depends on the particle shape andsurface texture. Corn starch particles being more uniformlyshaped and with smoother surface were more efficiently coatedwith the nano-silica particles than Avicel PH105 particles whichare irregular in shape and having rough surface texture. Also, fromthe images it was found that Aerosil R972 gave more efficientcoating as compared to Aerosil 200P.

3.2. Surface roughness determination of the compacts

The values for average surface roughness (Ra) and rmsroughness (Rrms) of pellets used for contact angle experiments(goniometric method) were calculated from AFM study (Table 3).

Fig. 2. Images of glycerol drop placed on t

All the pellet surfaces exhibited almost comparable roughnessvalues which were much below 100 nm. Since the averageroughness values for all the pellets were very less, these surfacescan be considered to be practically smooth with respect to thereported surface roughness values that affect contact anglemeasurements (Ryan and Poduska, 2008; Zografi and Johnson,1984). Results from AFM study thus eliminate the possibility ofinfluence of surface roughness factor on contact angle measure-ment using sessile drop method.

3.3. Wettability of powders by sessile drop contact angle method

Fig. 2 shows the image of the contact angle of glycerol dropplaced on different excipient surfaces at the end of 1 s. In all cases,it was found that contact angle of the Aerosil 200P coatedexcipients is less than corresponding uncoated excipients. Whencompared with the measured contact angle of Aerosil R972(hydrophobic) coated excipients and that of Aerosil 200P(hydrophilic) coated excipients, it was found that powders coatedwith former have higher contact angle (less wetting).

The static contact angle and the calculated work of adhesion(Wa) values obtained for all the three excipients are shown inTable 4. During the experiment with water as a test liquid, it wasobserved that drops placed on starch compacts were immediatelytaken up by the compacts and owing to the swelling behavior, thecontact angle determination for corn starch using water wasimpossible. However, with glycerol as a test liquid which is moreviscous and hence didn't penetrate into starch surface as quickly aswater, Aerosil 200P (hydrophilic) coated starch compacts showed asignificant decrease in the mean contact angle from 41.60� foruncoated compacts to 23.46� indicating increase in wettability ofits surface. Whereas for Aerosil R972 (hydrophobic) coatedcompacts, the mean contact angle increased to 50.95� signifyingincreased hydrophobicity (lower wetting behavior) of the surface.The work of adhesion of glycerol with uncoated starch compactsincreased from 111.88 mJ/m2 to 122.71 mJ/m2 for hydrophiliccoating whereas it decreased to 104.4 mJ/m2 for hydrophobic typeof nano-coating indicating more interaction between glycerol andhydrophilic nano-silica on the surface and increased wetting

he excipient surface at the end of 1 s.

Table 4Contact angle and work of adhesion for the excipient powders from sessile drop method.

Excipient Mean contact angle (�) Work of adhesion, Wa

(mJ/m2)

Water Glycerol Water Glycerol

Corn starch – 41.60 � 2.33 – 111.88 � 1.23Corn starch 200P coated – 23.46 � 1.04 – 122.71 � 0.37Corn starch R972 coated – 50.95 � 1.74 – 104.44 � 0.89Lactochem fine 0.0 � 0.0 19.84 � 2.32 145.6 � 0.0 124.16 � 0.84Lactochem fine 200P coated 0.0 � 0.0 17.49 � 1.23 145.6 � 0.0 125.03 � 0.42Lactochem fine R972 coated 34.2 � 2.55 28.2 � 2.22 132.98 � 1.82 120.37 � 1.15Avicel PH105 30.6 � 2.04 22.23 � 1.68 140.18 � 0.99 123.22 � 0.68Avicel PH105 200P coated 28.4 � 2.10 19.86 � 1.09 136.82 � 1.30 124.19 � 0.41Avicel PH105 R972 coated 40.0 � 1.71 24.88 � 2.8 128.52 � 1.45 122.02 � 1.33

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 357

behavior of starch. For lactochem fine samples, both uncoated andAerosil 200P coated surface resulted in zero contact angles withwater. This indicated a completely wetting nature of the surface.However, when the water drop was placed on the compact ofAerosil R972 coated lactochem fine, it showed a mean contactangle value of 34.2� due to hydrophobic nature of coating.Corresponding contact angle using glycerol was 19.84� foruncoated lactochem fine and that of Aerosil 200P coated andAerosil R972 coated lactochem fine were 17.49� and 28.2�

Fig. 3. Square of mass gain of water vs. time for uncoated and coated (a) corn starch,(b) lactochem fine and (c) Avicel PH105 powders.

respectively. The work of adhesion for uncoated and coatedlactose compacts showed similar trend as observed with cornstarch powders (Table 4). The changes in contact angle and work ofadhesion for surface modified Avicel PH 105 powders werecomparatively less prominent due to the poor quality of coatingachieved (observed from FESEM studies). In general, with increasein hydrophilic nature of the surface, the contact angle valuesdetermined using polar test liquids (de-ionized water or glycerol)decreased and vice versa with hydrophobic coating. Also, in allcases the work of adhesion for water was higher than that ofglycerol. This is because of higher surface tension of water thanglycerol (Table 1, Eq. (3)). Overall, the results showed that nano-coating resulted in the modification of surface wettabilitycharacteristics and by controlling the nature of coating (hydro-philic or hydrophobic), wettability characteristics of the powderscan be changed to the desirable extent. However, these changeswere found to be dependent on the quality of coating achieved,which in turn appears to be strongly dependent on type of nano-particle used for coating as well as on the morphology of hostparticles as described from FESEM results.

3.4. Wettability determination by liquid penetration method

Wettability of excipients from liquid penetration experiments isshown in Fig. 3. It was observed that as the water penetratethrough the powder bed, it gradually wets the particles. Fig. 3depicts the square of mass gain of water as a function of time for alluncoated and coated powders. The plots of mass square vs. timeshowed a linear relation for all the powder samples which wasfollowed by a saturation phase. However, variation in slope fordifferent powder samples indicated difference in the liquidpenetration rate which is dictated by the wettability characteristicsof the particle surface.

From Fig. 3a it can be seen that uncoated starch powder showedvery slow water penetration rate but it was still greater than thatobserved for hydrophobic coated corn starch. On the other hand,starch coated with hydrophilic silica showed extremely high massgain of water. Lactochem uncoated and those coated withhydrophilic silica powders found to have similar initial wateruptake (upto 20 s). However, after that it remained constant forformer (uncoated) reaching an almost equilibrium (Fig 3b). In caseof Avicel powders, similar trend for water penetration wasobserved with hydrophobic and hydrophilic coating (Fig.3c).However, the difference in the slopes of curves was found to beless between Avicel PH105 uncoated and coated powders due tolower surface coverage of nano-coating. In general, higherpenetration rates were observed for hydrophilic type of coatingand vice versa for hydrophobic coating for all powders. This can beexplained from the fact that during its penetration course throughthe powder bed, it encounters hydrophilic and hydrophobic

Table 5Contact angle, liquid penetration rate, material constant for solids from Washburn method and bulk densities of powders.

Powder Contact angle Liquid penetration rate Material constant,C x 10�14

Poured bulk density Tapped bulk density

(�) (g/s) (m5) (g/ml) (g/ml)

Starch Uncoated 84.55 � 2.4 0.016 � 0.00 1.142 � 0.24 0.40 � 0.02 0.65 � 0.01Starch 200P coated 78.45 � 1.75 0.035 � 0.00 0.996 � 0.03 0.59 � 0.02 0.72 � 0.00Starch R972 coated 85.57 � 2.01 0.009 � 0.00 0.512 � 0.08 0.64 � 0.01 0.79 � 0.01Lactochem uncoated 79.22 � 1.64 0.039 � 0.00 1.507 � 0.08 0.44 � 0.01 0.77 � 0.01Lactochem 200P coated 68.90 � 1.87 0.067 � 0.01 0.785 � 0.08 0.54 � 0.01 0.92 � 0.00Lactochem R972 coated 82.72 � 0.82 0.018 � 0.01 0.506 � 0.04 0.66 � 0.02 0.98 � 0.01Avicel PH105 uncoated 52.04 � 1.54 0.088 � 0.00 1.678 � 0.00 0.31 � 0.01 0.49 � 0.00Avicel PH105 200P coated 37.35 � 0.86 0.091 � 0.00 1.182 � 0.06 0.33 � 0.00 0.57 � 0.00Avicel PH105 R972 coated 58.13 � 1.02 0.058 � 0.00 0.980 � 0.07 0.36 � 0.01 0.62 � 0.01

358 V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363

particle surface. For hydrophilic type of coating, water encountersmajority of hydrophilic surface which increases the spreading ofwater within shorter duration of time. With hydrophobic type ofcoating, water encounters hydrophobic surface which decreaseswater spreading and slow penetration through the bed.

From the liquid penetration profiles obtained for differentpowders, contact angle values for water as test liquid wascalculated using modified Washburn equation (Eq. (2)). Table 5presents the calculated contact angle values, penetration ratescalculated from the slope linear portion of water absorption curveand material constant values along with the poured bulk andtapped bulk density obtained for uncoated and coated excipients. Itcan be observed that the material constant decreases after surfacemodification but the extent of decrease depends on the type ofcoating performed (Table 5). This can be attributed to the fact thatit depends on the powder packing properties as described inTable 5. As Aerosil R972 coated powders are more closely packed(achieved more poured and tapped density), material constant forthese excipients was found to be lowest followed by Aerosil 200Pcoating and highest for uncoated excipients. This variation in thematerials constant can influence the water penetration rate andwettability characteristics of powder.

3.5. Comparison of wettability determination methods

Comparison of contact angle values obtained from sessile dropmethod and Washburn method revealed a large difference in thesedata (refer Tables 4 and 5). For starch samples, as direct contactangle measurement using water was not possible hence forcomparison purpose contact angle values using glycerol as testliquid were referred. The difference in contact angle data wasfound to be even greater for corn starch and lactochem powderswhere coating was comparatively good. For all powders, contactangle values obtained from liquid penetration method (advancingcontact angle) were considerably higher than those obtained withsessile drop technique (static contact angle). This difference incontact angle from two methods is also widely reported inliterature (Chibowski and Hołysz, 1997; Grundke and Augsburg,2000). Also, it has been clearly reported in literature that contactangles obtained from Washburn method are usually an overesti-mation of those obtained from sessile drop method for the samesolids (Chibowski and Perea-Carpio, 2002). These differencesobserved was due to difference in measurement techniques.However, in spite of difference in absolute values of the contactangle, the wettability trend remained similar in both the cases.Hydrophilic coating resulted decrease in contact angle (higherwetting behavior) and hydrophobic coating resulted increase incontact angle (lower wetting behavior) with respect to thecorresponding values for uncoated powders.

As the contact angle from liquid penetration method is affectedby the factors such as particle morphology, bed porosity and

sample preparation method, most of the time the contact angledata from Washburn equation underestimates the surface energiesof the solids (Chibowski and Perea-Carpio, 2002). Hence, staticcontact angle values from sessile drop technique with glycerol astest liquid was used here for surface energy calculation.

3.6. Surface energy determination using contact angle approach

Fig. 4 shows the calculated surface energy plots for all theexcipient powders. A general trend of slight decrease in dispersivesurface energy (gs

d) and increase in polar surface energy (gsp) was

observed for Aerosil 200P coated powders. While decrease in gsd

can be attributed to the passivation of high energy sites (Han et al.,2013), the increase in gs

p can be explained from the hydrophilicnature of nano-particles which has hydroxyl groups on its surface(Rudiger, 2009). In case of coated starch powder (Fig. 4a), althoughgs

d decreased slightly from 45.13 mJ/m2 to 43.89 mJ/m2, there wasa significant increase of the polar surface energy from around 9 mJ/m2 for uncoated corn starch to 18 mJ/m2 for hydrophilic coatingresulting in an overall increase in total surface energy from54.5 mJ/m2 to 62.47 mJ/m2 (Fig. 4a). This is mainly because thehydroxyl groups present on Aerosil 200P interacts more with thepolar solvents causing increase in gs

p and consequent reduction incontact angles (discussed earlier). For Aerosil 200P coatedlactochem powder, a marginal decrease in gs

d from 46.43 mJ/m2

to 45.99 mJ/m2was observed whereas gsp increased from 16.70 mJ/

m2 to 19.34 mJ/m2. In case of Aerosil 200P coated Avicel powders,both gs

d and gsp remained more or less constant. The total surface

energy (gst) remained almost unchanged for lactochem (Fig. 4b)

and Avicel PH105 (Fig. 4c) powders coated with Aerosil 200P.For Aerosil R972 (hydrophobic) coated powders, a general trend

for the decrease in total surface energies was observed. This isbecause the hydrophobic coating resulted in decrease in thedispersive (gs

d) as well as polar components (gsp) of surface energy

for all the powders. A significant decrease in polar surface energy(gs

p) component for Aerosil R972 coated powders were observedwith an exception of Aerosil R972 coated Avicel PH105 (Fig. 4b) dueto poor quality of the coating. The gs

p decreased from 9.37 mJ/m2 to6.10 mJ/m2 and 16.70 mJ/m2 to 14.21 mJ/m2 for corn starch andlactochem powders respectively. This decrease in the polarcomponents can be explained from the fact that, hydrophobicsilica is synthesized by treatment of hydrophilic silica withdi-methyl di-chlorosilane which results hydrophobic alkyl chainson surface of hydrophilic silica particle (Rudiger, 2009). Thisreduces the interaction of surface with the polar liquids and thesurface became comparatively less wetting which is reflected incontact angle values with Aerosil R972 coated powders asindicated in Table 4.

Wettability of powders was also quantified using spreading of aliquid over a solid surface called as spreading co-efficient (Rowe,1989). Spreading coefficient of water and glycerol for excipient

Fig. 4. Polar, dispersive and total surface energies for (a) corn starch, (b) lactochemfine and (c) Avicel PH105 from sessile drop contact angle method.

Fig. 5. Spreading coefficient of polar liquids as a function of contact angle for (a)corn starch, (b) lactochem fine and (c) Avicel PH105.

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 359

surfaces were calculated (Eq. (4)) and plotted against the contactangle values obtained (Fig. 5). As depicted in Fig. 5, the spreadingco-efficient for the excipients varied with hydrophilic andhydrophobic nature of coating. While spreading co-efficientincreased for all the excipient powders with hydrophilic natureof nano-coating, it decreased for hydrophobic type of coating.Again, these variations in spreading co-efficient values were moreprominent with the excipients in which better quality coating wasachieved (as shown in FESEM studies). Also, in all the cases thecoefficient values for glycerol was found to be higher than those

obtained with water as a test liquid since glycerol has lower surfacetension as compared to water (refer Table 1). This was also evidentin work of adhesion data evaluated from contact angle data inTable 4.

3.7. Surface energy determination from Inverse gas chromatography

Fig. 6 depicts the dispersive, polar and total surface energies foruncoated and surface modified excipient powders at an infinitedilution of 3% probe surface coverage. Results showed that all the

360 V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363

nano-coated powders exhibited a general trend of decrease in thegs

d values and alteration in gsp component based on the nature of

nano-silica i.e., hydrophilic or hydrophobic.With Aerosil 200P coating the gs

d decreased from 48.03 mJ/m2

to 40.09 mJ/m2 for starch, 47.95 mJ/m2–41.65 mJ/m2 for lactochemand 47.17 mJ/m2–43.96 mJ/m2 for Avicel PH 105. On the other hand,the gs

p values increased from 6.55 mJ/m2 to 9.52 mJ/m2 for starch,9.02 mJ/m2–11.72 mJ/m2 for lactochem and 4.97–9.15 mJ/m2 forAvicel PH105. Thus, hydrophilic coating led to increase in gs

p

values for all excipients and decrease in gsd.

Fig. 6. Polar, dispersive and total surface energy from IGC method for (a) cornstarch, (b) lactochem fine and (c) Avicel PH105.

Fig. 7. Contact angle of glycerol as a function of polar surface energy of corn starch,lactochem fine and Avicel PH105 obtained from IGC.

Aerosil R972 coating also showed similar trends in dispersivecomponents of surface energy of all excipients as observed withAerosil 200P coated powder. The gs

d decreased to 37.5 mJ/m2and36.75 mJ/m2for starch and lactochem respectively as compared togs

d of these uncoated powders (mentioned above). For Avicel PH105, the gs

d found to decrease from 47.17 mJ/m2 to 43.86 mJ/m2.The gs

p values for starch and Avicel PH105 showed very littledecrease with respect to lactochem coated powders which showeddecrease from 8.9 mJ/m2 to 3.85 mJ/m2. Thus, Aerosil R972 wasfound to be more effective in reducing the dispersive component ofsurface energy whereas Aerosil 200P was found to be moreeffective in increasing the polar surface energy of all excipients.These observations are consistent with the surface energycalculated form sessile drop experiments in terms of their trendsobserved with different types of coatings.

Overall, for the same nano-particle, the quality of nano-coatingvaried depending on the type of the excipients and their surfacemorphology which was further reflected in the surface energyresults obtained for different powders.

3.8. Comparison of surface energy determination from contact angleand IGC methods

Comparison of the surface energy values calculated fromcontact angle data and IGC approach for uncoated and coatedpowders revealed that values obtained from both the methodsfollowed similar rank order. Consistent to the previous studiesgiven in literature, not much difference in gs

d values wereobserved from two different methods (Dove et al., 1996). However,it should be noted that IGC results showed greater decrease in gs

d

values as compared to the values obtained from contact angleapproach for both Aerosil 200P and Aerosil R972 coating.Interestingly, in most of the cases gs

p values obtained fromcontact angle approach were considerably higher than thoseobtained from IGC studies. These differences in the magnitude ofsurface energy components of uncoated and coated powders canbe due to difference in the nature and treatment of the test samplesunder study and also due to difference in the theoreticalapproaches used for surface energy calculation. In contact anglemethod, powders were compressed to form compacts whereas thepowder samples required no treatment for IGC experiments. Also,it can be said that the contact angle approach provides the surface

Fig. 8. FESEM images of (a) 0.25% Aerosil R972 coated, (b) 0.5% Aerosil R972 coated and (c) 1.0% Aerosil R972 coated.

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 361

energy information which is averaged over a larger surface area (atmacroscopic level) as the liquid spreads and interacts over solidsurface, whereas surface energy determination using IGC atinfinite dilution provides information from only limited butsignificantly active sites on the surface. Overall, both thetechniques used for surface energy determination of solids wereable to gauge similar type of changes in surface energetics ofpowders before and after surface modification.

3.9. Wettability and polar surface energy

As polar surface energy plays a crucial role towards surfacewetting of a solid, polar component of surface energy obtainedfrom IGC results was correlated to the contact angles using sessiledrop technique. Fig. 7 shows the contact angle obtained withglycerol as test liquid for all excipients as a function of polar surfaceenergy (gs

p) determined from IGC experiments. As expected, withincrease in gs

p contact angle decreased for all excipients. From theresults obtained, uncoated lactochem fine powder was found tohave highest polar surface energy followed by corn starch and leastpolar surface energy for Avicel PH105. The variations in contactangle values after nano-coating were most prominent for coatedcorn starch and lactochem fine powders where quality of thecoating was comparatively better. The lowest variation wasobserved with Avicel PH105 powders due to low level of coating

achieved. The plot shows that Aerosil 200P coated powders mostlyoccupy the lower-right bottom region of the plot whereas theAerosil R972 coated powders moves towards the upper-left regionof the plot indicating enhancement and reduction of wettingbehavior respectively based on the nature of coating. This isbecause of hydrophilic type of coating with Aerosil 200P consistingof higher polar functional groups led to increase in gs

p of theexcipients which in turn reduced the contact angle. These resultssuggest that the polar component of surface energy can beinversely correlated to the contact angle values i.e., higher gs

p

relates to lower contact angle.

3.10. Contact angle and surface energy as a function of level of nano-coating

FESEM images for starch powders with different level of AerosilR972 coating are shown in the Fig. 8. It can be seen from the imagesthat the 0.25% w/w coating was less dense than that of the coatingobserved at 0.5% w/w and 1.0% w/w levels.

Surface area coverage calculated through image processingconfirmed the observations from FESEM study. For 0.25% w/wnano-coating level, the surface area coverage was found to be onthe lower side of about 18.5%. On the other hand, the surface areacoverage for 0.5% w/w and 1.0% w/w levels were found to be in thesimilar range of around 53% and 57%, respectively.

Fig. 9. Work of adhesion and surface energy components as a function of nano-coating surface coverage for Aerosil R972 coated starch powders.

362 V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363

Fig. 9a and b depicts the work of adhesion (Wa) as a function ofsurface coverage of nano-coating with hydrophobic silica on cornstarch particles. It can be seen that, with the increase in % of surfacecoating, Wa decreased gradually indicating incremental non-wetting behavior due to increased hydrophobicity of the surface.From Fig. 9 it can be observed that at higher levels of surfacecoverage (above 50%) Wa was found to be sensitive to a verysmall change in surface coverage as seen for 0.5% w/w and 1.0% w/w coated sample. Small increment in surface coverage from 53% to57% led to decrease in Wa from 104.44 mJ/m2 to 89.71 mJ/m2 (i.e.,increase in contact angle and decrease in wetting behavior). Thisindicates that even a small change in the particle surface cansignificantly affect its wetting properties at higher level of surfacecoating.

Fig. 9a and b shows the changes in polar and dispersive surfaceenergies as a function surface coverage. The polar as well as thedispersive surface energy showed a gradual decrease from 6.55 mJ/m2 to 3.39 mJ/m2 and from 48.10 mJ/m2 to 35.92 mJ/m2 respec-tively as the coating level increased from 0% w/w to 1% w/w. Theprogressive decrease in dispersive surface energies is because athigher coating levels, plugging of the high energy sites on particlesurfaces will occur and thus the non-polar and polar probes cannow interact either with the nano-silica which has lowerdispersive component (Chen et al., 2010) or with other lowerenergy sites on the starch particle resulting in the decrease in theoverall dispersive and polar components of surface energy. Thisindicates that the different nano-coating levels used here, rangingfrom 0.25% w/w to 1% w/w, did influence the overall surface energyand contact angle values. Hence, based on the nature and level ofsurface coverage, desired surface wetting and energetic can beachieved.

4. Conclusion

The present work describes the influence of surface modifica-tion using nano-coating on surface characteristics of threepharmaceutical excipient powders viz. Avicel PH 105, lactochemfine powder and corn starch. Dry coating of excipients wasperformed using hydrophilic (Aerosil 200P) and hydrophobic

(Aerosil R972) colloidal silicon-di-oxide as guest particle. Thewetting behavior of powder surface was assessed from both staticand advancing contact angle measurements using sessile dropmethod and liquid penetration (Washburn method) methodrespectively. The polar (gs

p) and dispersive (gsd) components of

surface energies were determined from extended Fowke'sequation using static contact angle data and inverse gaschromatography (IGC) technique at infinite dilution. The resultsshowed that Washburn method provided comparatively highercontact angle values as compared to the sessile drop technique forthe same samples. However, both these techniques were able todifferentiate successfully the changes in hydrophilicity andhydrophobicity of surfaces with the nature of nano-particles usedfor coating. Wettability assessed in terms of spreading co-efficientof polar liquids on excipient surfaces indicated that Aerosil 200Pfacilitated spreading of liquids due to increased polarity of thesurface. This resulted in higher work of adhesion and greaterspreading co-efficient. In contrast, Aerosil R972 coating preventedspreading which was reflected by reduced value of spreadingcoefficient and work of adhesion. Analysis of surface energy valuesshowed a general trend of decrease in dispersive surface energy forall the surface modified powders due to passivation of most activesites on the surface. However, depending on the nature of thefunctional groups present in nano-silica, gs

p was found to behigher or lower for hydrophilic and hydrophobic coating respec-tively. Results also showed that wettability increase with increas-ing the polar component of the surface energy. Both the techniquesfor surface energy determination provided comparable and similartrends in gs

p and gsd components of surface energies for uncoated

and nano-coated excipients. gsd values from sessile drop and IGC

methods were found in the similar range. However, calculated gsp

values from contact angle approach showed comparatively highervariations than corresponding measured value of gs

p from IGC. Thestudy also successfully demonstrated that surface wettability andenergetics of powders can be modified by varying the level ofsurface coating for various process requirements in pharmaceuti-cal or other powder operations.

Acknowledgements

We acknowledge IITGN for financial support for this work andEvonik Degussa Industries for providing nano-silica as a giftsample for this research. We would also like to acknowledgeManish Thakkar from Shah Schulman Centre for Surface Scienceand Nanotechnology for helping with the contact angle experi-ments.

References

Buckton, G., Beezer, A.E., 1988. A microcalorimetric study of powder surfaceenergetics. Int. J. Pharm. 41, 139–145.

Buckton, G., Choularton, A., Beezer, A.E., Chatham, S.M., 1988. The effect of thecomminution technique on the surface energy of a powder. Int. J. Pharm. 47,121–128.

Buckton, G., Gill, H., 2007. The importance of surface energetics of powders for drugdelivery and the establishment of inverse gas chromatography. Adv. Drug Deliv.Rev. 59, 1474–1479.

Chen, Y., Jallo, L., Quintanilla, M.A.S., Dave, R., 2010. Characterization of particle andbulk level cohesion reduction of surface modified fine aluminum powders.Colloids Surf. A Physicochem. Eng. Asp. 361, 66–80.

Chibowski, E., Hołysz, L., 1997. On the use of Washburn’s equation for contact angledetermination. J. Adhes. Sci. Technol. 11, 1289–1301.

Chibowski, E., Perea-Carpio, R., 2002. Problems of contact angle and solid surfacefree energy determination. Adv. Colloid Interface Sci. 98, 245–264.

Das, S.C., Larson, I., Morton, D.A.V., Stewart, P.J., 2011. Determination of the polar andtotal surface energy distributions of particulates by inverse gas chromatogra-phy. Langmuir 27, 521–523.

Dove, J.W., Buckton, G., Doherty, C., 1996. A comparison of two contact anglemeasurement methods and inverse gas chromatography to assess the surfaceenergies of theophylline and caffeine. Int. J. Pharm. 138, 199–206.

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 363

Gamble, J.F., Davé, R.N., Kiang, S., Leane, M.M., Tobyn, M., Wang, S.S.Y., 2013.Investigating the applicability of inverse gas chromatography to binarypowdered systems: an application of surface heterogeneity profiles tounderstanding preferential probe-surface interactions. Int. J. Pharm 445, 39–46.

Ghoroi, C., Gurumurthy, L., McDaniel, D.J., Jallo, L.J., Davé, R.N., 2013a. Multi-facetedcharacterization of pharmaceutical powders to discern the influence of surfacemodification. Powder Technol. 236, 63–74.

Ghoroi, C., Han, X., To, D., Jallo, L., Gurumurthy, L., Davé, R.N., 2013b. Dispersion offine and ultrafine powders through surface modification and rapid expansion.Chem. Eng. Sci. 85, 11–24.

Grundke, K., Augsburg, A., 2000. On the determination of the surface energetics ofporous polymer materials. J. Adhes. Sci. Technol. 14, 765–775.

Han, X., Ghoroi, C., To, D., Chen, Y., Davé, R., 2011. Simultaneous micronization andsurface modification for improvement of flow and dissolution of drug particles.Int. J. Pharm. 415, 185–195.

Han, X., Ghoroi, C., Davé, R., 2012. Dry coating of micronized API powders forimproved dissolution of directly compacted tablets with high drug loading. Int.J. Pharm. 442, 74–85.

Han, X., Jallo, L., To, D., Ghoroi, C., Davé, R., 2013. Passivation of high-surface-energysites of milled ibuprofen crystals via dry coating for reduced cohesion andimproved flowability. J. Pharm. Sci. 102, 2282–2296.

Heng, J.Y.Y., Thielmann, F., Williams, D.R., 2006. The effects of milling on the surfaceproperties of form I paracetamol crystals. Pharm. Res. 23, 1918–1927.

Jallo, L.J., Ghoroi, C., Gurumurthy, L., Patel, U., Davé, R.N., 2012. Improvement of flowand bulk density of pharmaceutical powders using surface modification. Int. J.Pharm. 423, 213–225.

James, J., Crean, B., Davies, M., Toon, R., Jinks, P., Roberts, C.J., 2008. The surfacecharacterisation and comparison of two potential sub-micron sugar bulkingexcipients for use in low-dose, suspension formulations in metered doseinhalers. Int. J. Pharm. 361, 209–221.

Lefebvre, G., Galet, L., Chamayou, A., 2011. Dry coating of talc particles: effect ofmaterial and process modifications on their wettability and dispersibility.AIChE J. 57, 79–86.

Luner, P.E., Babu, S.R., Mehta, S.C., 1996. Wettability of a hydrophobic drug bysurfactant solutions. Int. J. Pharm. 128, 29–44.

Mujumdar, A., Wei, D., Dave, R.N., Pfeffer, R., Wu, C.-Y., 2004. Improvement ofhumidity resistance of magnesium powder using dry particle coating. PowderTechnol. 140, 86–97.

Mullarney, M.P., Beach, L.E., Davé, R.N., Langdon, B.A., Polizzi, M., Blackwood, D.O.,2011. Applying dry powder coatings to pharmaceutical powders using a comilfor improving powder flow and bulk density. Powder Technol. 212, 397–402.

Newell, H.E., Buckton, G., Butler, D.A., Thielmann, F., Williams, D.R., 2001. The use ofinverse phase gas chromatography to measure the surface energy of crystalline,amorphous, and recently milled lactose. Pharm. Res. 18, 662–666.

Rudiger, N., 2009. Technical Bulletin Fine Particles: Aerosil Fumed Silica forSolvent-Free Epoxy Resins. Evonic.

Ouabbas, Y., Dodds, J., Galet, L., Chamayou, A., Baron, M., 2009. Particle–particlecoating in a cyclomix impact mixer. Powder Technol. 189, 245–252.

Owens, D.K., Wendt, R.C., 1969. Estimation of the surface free energy of polymers.J. Appl. Polym. Sci. 13, 1741–1747.

Pepin, X., Blanchon, S., Couarraze, G., 1997. A new approach for determination ofpowder wettability. Int. J. Pharm. 152, 1–5.

Pfeffer, R., Dave, R.N., Wei, D., Ramlakhan, M., 2001. Synthesis of engineeredparticulates with tailored properties using dry particle coating. Powder Technol.117, 40–67.

Planinsek, O., Trojak, A., Srcic, S., 2001. The dispersive component of the surface freeenergy of powders assessed using inverse gas chromatography and contactangle measurements. Int. J. Pharm. 221, 211–217.

Puri, V., Dantuluri, A.K., Kumar, M., Karar, N., Bansal, A.K., 2010. Wettability andsurface chemistry of crystalline and amorphous forms of a poorly water solubledrug. Eur. J. Pharm. Sci. 40, 84–93.

Ramlakhan, M., Wu, C.Y., Watano, S., Dave, R.N., Pfeffer, R., 2000. Dry particle coatingusing magnetically assisted impaction coating: modification of surfaceproperties and optimization of system and operating parameters. PowderTechnol. 112, 137–148.

Rowe, R.C., 1989. Polar/non-polar interactions in the granulation of organicsubstrates with polymer binding agents. Int. J. Pharm. 56, 117–124.

Ryan, B.J., Poduska, K.M., 2008. Roughness effects on contact angle measurements.Am. J. Phys. 76, 1074.

Siebold, A., Nardin, M., Schultz, J., Walliser, A., Oppliger, M., 2000. Effect of dynamiccontact angle on capillary rise phenomena. Colloids Surf. A Physicochem. Eng.Asp. 161, 81–87.

Siebold, A., Walliser, A., Nardin, M., Oppliger, M., Schultz, J., 1997. Capillary rise forthermodynamic characterization of solid particle surface. J. Colloid Interface Sci.186, 60–70.

Tay, T., Morton, D.A.V., Gengenbach, T.R., Stewart, P.J., 2012. Dissolution of a poorlywater-soluble drug dry coated with magnesium and sodium stearate. Eur. J.Pharm. Biopharm. 80, 443–452.

Thakker, M., Karde, V., Shah, D.O., Shukla, P., Ghoroi, C., 2013. Wettabilitymeasurement apparatus for porous material using the modified Washburnmethod. Meas. Sci. Technol. 24, 125902.

Van Oss, C.J., Giese, R.F., Li, Z., Murphy, K., Norris, J., Chaudhury, M.K., Good, R.J.,1992.Determination of contact angles and pore sizes of porous media by column andthin layer wicking. J. Adhes. Sci. Technol. 6, 413–428.

Washburn, E.W., 1921. The dynamics of capillary flow. Phys. Rev. Lett. 17, 273–283.Zhou, Q.T., Qu, L., Larson, I., Stewart, P.J., Morton, D.A.V., 2010. Improving

aerosolization of drug powders by reducing powder intrinsic cohesion via amechanical dry coating approach. Int. J. Pharm. 394, 50–59.

Zisman, W., 1964. Contact angle, wettability and adhesion. Am. Chem. Soc.Zografi, G., Johnson, B.,1984. Effects of surface roughness on advancing and receding

contact angles. Int. J. Pharm. 22, 159–176.