Influence of surface modification on wettability and surface energy characteristics of pharmaceutical excipient powders.

International Journal of Pharmaceutics 475 (2014) 351–363

Contents lists available at ScienceDirect

International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm

Influence of surface modification on wettability and surface energy characteristics 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

A B S T R A C T

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

Influence of surface modification on wettability and surface energy characteristics of three micron size pharmaceutical excipient powders was studied using hydrophilic and hydrophobic grades of nano-silica. The wetting behavior assessed from contact angle measurements using sessile drop and liquid penetration (Washburn) methods revealed that both techniques showed similar wettability characteristics for all powders depending on the hydrophilic or hydrophobic nature of nano-coating achieved. The polar (g sp) and dispersive (g sd) components of surface energies determined using extended Fowke’s equation with contact angle data from sessile drop method and inverse gas chromatography (IGC) at infinite dilution suggested a general trend of decrease in g sd for all the surface modified powders due to passivation of most active sites on the surface. However, depending on the nature of the functional groups present in nano-silica, g sp was found to be either higher or lower for hydrophilic or hydrophobic coating respectively. Results show that wettability increases with increasing g sp. Both the techniques of surface energy determination provided comparable and similar trends in g sp and g sd components of surface energies for all excipients. The study also successfully demonstrated that surface wettability and energetics of powders can be modified by varying the level of surface coating. ã 2014 Elsevier B.V. All rights reserved.

Keywords: Contact angle Surface wettability Surface energy Spreading co-efficient Work of adhesion

1. Introduction Surface characterization of the solid provides better understanding of their behavior in different processes. Surface wettability and surface energetics of powders are most critical properties to be taken into consideration during formulation and development of a solid and liquid dosage forms in pharmaceutical industry. Changes in wettability characteristics of powders can have significant effect on pharmaceutical processes such as granulation, disintegration, dissolution, dispersibility etc. Similarly, surface energy of powder plays an important role in determining the physicochemical properties such as wettability, adhesion, flowability, packing etc. Both surface wettability and energetics are prone to physical or chemical changes occurring on the solid surface. While wettability can be predominantly affected by the chemical nature of surfaces, the surface energy can be affected by various factors like powder processing or handling conditions,

* Corresponding author. Tel.: +91 793 245 9897; fax: +91 792 397 2583. E-mail addresses: [email protected], [email protected] (C. Ghoroi). http://dx.doi.org/10.1016/j.ijpharm.2014.09.002 0378-5173/ ã 2014 Elsevier B.V. All rights reserved.

environmental conditions, particle size (Buckton et al., 1988; Han et al., 2013) etc. In pharmaceutical industry, the conventional method employed for surface modification of solids includes applying solvent based functional polymer coating. Surface modification through dry coating 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 (Pfeffer et al., 2001). It involves mechanical force where nano-particles are first de-agglomerated and then dispersed on to the surface of host particle. Dry particle coating being a solventless technique offers large number of advantages over the conventional solvent based techniques for property modification of powders. Owing to its simplicity and cost effectiveness, dry coating technique is becoming popular among the scientific community for modifying particle surface properties. Various researchers have employed this technique of particle surface modification for different applications which include improving powder flow (Jallo et al., 2012), fluidization (Ghoroi et al., 2013a), dispersion (Ghoroi et al., 2013b), aerosolization (Zhou et al., 2010), dissolution (Han et al., 2011, 2012; Tay et al., 2012) and also for modifying wettability characteristics (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 angle determination is one of the most commonly used methods. It can be determined using different approaches such as sessile drop technique (Luner et al., 1996), liquid penetration method (Washburn method) (Washburn, 1921), Wilhelmy method (Pepin et 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 and dispersibility of talc powders which were dry coated with hydrophobic silica particles in Cyclomix high shear mixer. They used sessile drop method for wettability measurement and found that concentration of nano-particle and processing time both affect the wettability. They observed that work of adhesion calculated from contact angle influenced the dispersion rate of talc powder in water. Similarly, Ouabbas et al. (2009) used Cyclomix high shear mixer for surface modification of silica gel and corn starch particles by dry coating with different percent w/w of magnesium stearate and different grades (hydrophobic and hydrophilic) of fumed silica respectively. The wettability was studied by the sessile drop method and dynamic vapor sorption (DVS) measurements. The results indicated that dry coating of silica gel powder by hydrophobic magnesium stearate resulted in improvement of its hydrophobic properties. The moisture adsorption–desorption isotherms of uncoated and coated particles obtained from dynamic vapor sorption analyzer also suggested altered moisture adsorption and desorption characteristics of powders (Ouabbas et al., 2009). Similarly, for assessment of surface energetics of solids, there are various techniques available such as techniques based on wettability determination like contact angle determination using sessile drop method (Luner et al., 1996; Puri et al., 2010) or liquid penetration method (Siebold et al., 1997), techniques based on gas adsorption phenomenon like inverse gas chromatography (IGC) (Das et al., 2011; Newell et al., 2001) and based on thermodynamic principles like microcalorimetry (Buckton and Beezer, 1988). While contact angle method has been widely used (mostly compressed disc technique) to evaluate the surface characteristics of solids (James et al., 2008; Luner et al., 1996), in recent years IGC has been considered as a more accurate and sensitive alternative for surface energy determination (Buckton and Gill, 2007). Different studies comparing the surface energy determined from these two methods suggested a great degree of agreement for dispersive component of the surface energy (Dove et al., 1996; Heng et al., 2006; Planinsek et al., 2001). Dove et al. (1996) studied the wettability and surface energetics of theophylline and caffeine powders from contact angle and inverse gas chromatography (IGC) methods respectively. They found that dispersive component of surface energies obtained from IGC was almost identical to that from contact angle method. Dispersive surface energies of pharmaceutical powders were also compared from these two different approaches by Planinsek et al. (2001). They also suggested that a good correlation of results for these methods can be obtained provided diiodomethane or bromonaphthalene is used to determine the non-polar components in contact angle studies. In all these studies, the dispersive component of surface energy was found to be comparable from both the techniques. However, analysis based on polar component of surface energy has still not been discussed in literature. Thus, a direct comparison of polar component of surface energy, which otherwise has a great significance for complete characterization of solid surface energetics is missing in the literature. Although numerous studies have reported the comparative accounts for wettability property from different methods, a comprehensive study of wettability and surface energetic properties together from different methods and

their interrelation is lacking in open literature. This work is planned to compare wettability and surface energy of powders separately from two different techniques. A comprehensive analysis of these results based on the morphological aspects and chemical nature of particle surfaces is also planned. With this aim, the influence of surface modification on wettability and surface energetics of three commonly used excipient powders viz. Avicel PH 105, lactochem fine powder and corn starch was assessed before and after their surface modification using hydrophilic and hydrophobic colloidal silica nano-particles. Also, the effect of surface morphology on quality of the surface modification for these fine powders was studied. The wettability of coated and uncoated powders was evaluated through contact angle measurement using sessile drop and liquid penetration methods. The wettability characteristics were also explained in terms of work of adhesion and spreading coefficient. Surface energy of these powders was determined using contact angle data from sessile drop method and from IGC at infinite dilution. Results for both wettability and surface energy determined from different methods were then compared and correlated. The extent of surface modification and its effect on wettability and surface energetics of the powder was also studied using corn starch powder with different percentage of hydrophobic 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’ powders for nano-coating. Hydrophilic fumed silica grade (Aerosil 200P) and hydrophobic fumed silica grade (Aerosil R972 Pharma) having mean particle size of around 12 nm and 16 nm respectively were obtained as a gift sample from Evonik/Degussa Industries, USA and were selected as ‘guest’ particle for nano-coating. De-ionized water (Milipore, USA) and glycerol (Merck, USA) were used as polar test liquids; and diiodomethane (National Chemicals, India) and n-hexane (Merck, USA) were used as non-polar probe for contact angle determination studies. For inverse gas chromatography experiments Decane (Spectrochem, India), Nonane (Merck, USA), Octane (Spectrochem, India) and Heptane (RANKEM, India) were used 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 hydrophobic grades of nano-silica following a method described in the literature (Mullarney et al., 2011). Co-mill provides intensive mixing between the host (excipient) and guest (nano-silica) particles with the help of impellers resulting in coating of the host surfaces with guest particles. Prior to coating experiment, the excipient powder and nano-silica were co-sifted through 30 mesh BSS sieve and pre-mixed in V-blender at 15 1 rpm for 10 min. The blend was then passed through Co-mill operating at 1800 1 rpm to achieve the required coating. Based on the bulk property characterization previously performed in the lab, about 0.5% w/w level of Aerosil R972 (hydrophobic) and 1.0% w/w level of Aerosil 200P (hydrophilic) were used for coating all three excipients. Further, to study the effect of percentage of surface area coverage on wettability and surface energy, only corn starch was coated with 0.25%, 0.5% and 1% w/w of Aerosil R972. All the experiments were performed at room conditions of 40 5% RH and 25 2 C.


2.3. Particle size and morphology To investigate any change on the particle size of the coated excipients due to the co-milling process employed for dry coating purpose, laser diffraction particle size analyzer (Cilas, Model 1190) was used for the particle size determination of uncoated and dry coated excipient powders using dry analysis mode (air dispersion mode). The mean and median diameters (d50) of powder samples were determined at an air dispersion pressure of 1 bar. The surface morphology for uncoated and nano-coated excipient samples were examined using field emission scanning electron microscope (FESEM) (JEOL JSM 7600 F, USA). The FESEM analysis was done with working distance (WD) of 4.5–6.0 mm and a voltage of 1.5–2.0 kV. All coated and uncoated powder samples were then studied for their wettability and surface energetics. 2.4. Wettability determination studies Wettability determination was carried out with two methods viz. sessile drop method using water, glycerol as polar liquids and diiodomethane as non-polar liquid; and liquid penetration method (Washburn method) using water as polar and n-hexane as nonpolar liquid. 2.4.1. Wettability studies using sessile drop method The contact angle for the excipient samples were determined directly using sessile drop goniometric method. For these experiments, flat surfaces of the excipient powders were formed by preparing discs (pellets) on IR Press. About 200 mg of excipient powders were taken and compressed at 2 t pressure to get pellet of 13 mm diameter. All the prepared compacts were stored in air tight containers prior to the experiments. As surface roughness plays an important role in wettability studies using contact angle measurements (Ryan and Poduska, 2008), AFM (Nanoscope, Bruker) studies were carried out so as to determine surface roughness of the excipient pellets. A scan size of 5 m 5 m was used to obtain the AFM images for surface roughness determination studies. AFM images obtained were then analyzed using nanoscope software to report the average roughness (Ra) and rms roughness (Rrms) values from three different regions of the compacts. Contact angles measurement was performed by goniometric method using polar liquids water and glycerol; and non-polar liquid diiodomethane. The details of surface tension property of test liquids are given in the Table 1. The contact angles were measured using Theta Optical Tensiometer (KSV Instruments) consisting of a sample stage, light source, lens and image capture camera. A small drop of liquid was placed on the surface of the pellet using a syringe and the drop images were captured using high speed camera at 0.02 s intervals of time. The drop volume of approximately 2 ml for water, 6 ml for glycerol and 0.5 ml for diiodomethane were used for the measurements. Mean contact angle was determined directly from the captured images by measuring the angle formed between the solid and the tangent to the drop surface with the help of Attension Theta software.

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

Polar component,

Total,

(mN/m)

(mN/m)

(mN/m)

21.8 34 50.8

51 30 0

72.8 64 50.8

g ld

Water Glycerol Di-iodomethane

g lp

g lt

353

Measurements using the above mentioned liquids were repeated on different surfaces of the same material which were then averaged. All the measurements were performed at the room temperature of 25 2 C and a relative humidity of 40 5%. The affinity of liquid for a solid surface can also be quantified using work of adhesion (Zisman, 1964) which represent the work required to extract a drop of the test liquid from a solid surface. Work of adhesion (Wa) between a liquid and solid (compacts) was determined from the surface energy value of liquid (g lt) and contact angle (u) obtained by goniometric method using Eq. (1). W a ¼ g l t ð1 þ cos u Þ

(1)

The greater the work of adhesion; more is the interaction between liquid and solid surface that is, surface is more wetting in nature. 2.4.2. Wettability studies using liquid penetration method In addition to the static contact angle measurement using sessile drop method, the advancing contact angle as well as liquid penetration rate was determined using an experimental setup to measure the mass gain of liquid in powder bed as a function of time. The apparatus and the experimental procedure used was similar to that described by Thakker et al. (2013). The assembly consisted of a sample holder in the form of a cylindrical metallic tube, perforated at the bottom and hanged to a microbalance hook from the top. A Petri dish containing the test liquid was placed just below the perforated end of the holder on a mechanical platform. A filter paper was placed at the perforated end of the sample holder to support the powder sample. About 2 g of sample was filled and packed uniformly using an automatic tapper (Veego Instruments Corporation, TAP/MATIC-II model, India). The test liquid was then gradually brought into contact with perforated end of the tube with the help of a manual jack and the mass gain vs. time was recorded. A combination of test liquid (deionized water) and a standard completely wetting liquid (n-hexane) was used for the wettability determination experiments. All the experiments were performed in triplicates at 25 2 C and between each experimental run the sample holder was cleaned and dried thoroughly. The contact angles for different liquid and powder systems were determined using modified Washburn equation which provides relationship between liquid penetration rate and contact angle (u) as given below h (2) M2 T¼ 2 Cr g l cos u 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 material constant which depends on powder bed porosity (e), equivalent pore radius (rc) and powder packing radius (R) as given by Eq. (3), C¼

rc e2 ðpR2 Þ2 2

(3)

For the determination of advancing contact angle from modified Washburn method, only the linear part of mass square vs. time curve was used for calculations. Also, considering the flow instabilities reported in literature at the initial wetting stage (Siebold et al., 2000, 1997), the time points only after 10 s from the initial contact were used for calculation purpose. In general, higher slope of mass square vs. time curve indicates lower contact angles implying higher wettability. The penetration rate (dM/dt) was also calculated for each powder sample. As material constant (C) depends on powder packing, the poured and tapped density of the powder was determined using conventional graduated cylinder method and automatic tapped density apparatus. These results correlated with the material constant values (C). The powder sample was gently filled in a

354


100 ml glass cylinder while keeping the cylinder in a slightly inclined position so as to avoid the compaction of the powder during free fall. The poured volume and mass of powder were noted. The tap density of powder samples were determined using a tap density test apparatus (Veego Instruments Corporation, TAP/ MATIC-II model, India) employing USP type I test in which the cylinder is raised by a height of 14 2 mm and then allowed to drop under its own weight. The cylinder was tapped at a nominal rate of 300 taps per minute for a minimum of 1250 taps (500 initial taps followed by final 750 taps). The tapping was continued till a tapped volume difference of less than 2% was obtained between 2 consecutive tapping sequences. 2.5. Surface energy determination studies Surface energy of excipient powders were calculated using the contact angle readings obtained from the goniometric method (sessile drop method) as well as from IGC at infinite dilution. These methods are described below. 2.5.1. Surface energy determination from contact angle approach Owens–Wendt–Kaelble model also termed as extended Fowke’s model based on the Young–Dupree equation was used for the surface free energy calculations of solid under study (Owens and Wendt, 1969). This two liquid approach for solid surface energy determination utilizes the relationship between contact angle and dispersive (g d) and polar (gp) components of liquid and solid surface energies as shown in Eq. (4). qffiffiffiffiffiffiffiffiffiffiffiffi qffiffiffiffiffiffiffiffiffiffiffiffi (4) g l t ð1 þ cosuÞ ¼ 2ð g pl g ps þ g dl g ds where g lt, g ld and g lp are the total, dispersive and polar surface energies of liquid whereas g sd and g sp are the dispersive and polar components of solid surface energy respectively. The dispersive (g sd) component of solid surface energy can be determined using a non-polar liquid so that the above equation can be modified to the equation given below

g ds ¼

g dl ð1 þ cos uÞ2

(5)

4

Putting the value of g sd calculated from Eq. (5), Eq. (4) provides the value for g sp. Finally, the total surface energy (g st) of solid which is the sum of dispersive (g sd) and polar (g sp) components was calculated. Surface energy studies from contact angle approach can also be used to extract some additional information related to the wettability characteristics of a solid surface with the help of a thermodynamically determined co-efficient called as spreading co-efficient. Spreading co-efficient (Sl/s) is an index of spreading of a liquid over a solid surface and it can be determined from their respective dispersive (g d), polar (g p) and total (g t) surface energy values using Eq. (6) (Rowe, 1989). Increase in spreading coefficient

of a liquid on a solid indicates increase in wettability of solids. 2 g sdgld g spg lp þ (6) Sl=s ¼ t gl g sd þ g ld g sp þ glp 2.5.2. Surface energy determination from IGC method Additionally, surface energy determination experiments were carried out using an IGC surface energy analyzer (Surface Measurement Systems, London, UK). The uncoated and coated powders were carefully packed into individual pre-silanized glass columns (300 mm length and 3 mm I.D.) and plugged with silanized glass wool (Sigma–Aldrich, UK) at both the ends of column. Proper sample packing in the column was ensured with the help of jolting voltameter (Surface Measurement Systems, London, UK) which provides mechanical tapping to the column so as to remove the voids in packed sample bed. Individual sample columns were then separately mounted into column oven with the required column fittings. The surface energies of uncoated and surface modified powders were determined at 0% RH and 30 C column conditions. Each column was allowed to undergo a conditioning cycle at the set test conditions for a period of 1 h prior to the actual analysis. The surface energy analyses of the samples were carried out at an infinite dilution (fixed probe coverage of 3%) of the non-polar and polar probes. Helium was used as a carrier gas with a flow rate of 10 ml/min and methane was used as a reference gas for the injections. The surface energy determination experiments were carried out on two columns for each 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 nanocoating on wettability and surface energetics, corn starch was coated with 0.25% w/w, 0.5% w/w and 1% w/w of nano-silica using dry coating method. The percent surface area coverage was determined experimentally from image processing of FESEM images of coated particles using ImageJ 1.47 software and correlated with the wettability and surface energy characteristics of 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-silica coated excipients are presented in Table 2. Both the uncoated and coated excipient powders showed almost similar particle size. Therefore, it can be implied that intensive mixing and impaction forces applied during the coating process in the mixing zone of the cone mill did not reduce the particle size of the powders.

Table 2 Mean and median diameters of uncoated and nano-coated powders. Excipient (host material)

Guest particle coating

d50(mm)

Mean(mm)

Corn starch Corn starch Corn starch Lactochem fine Lactochem fine Lactochem fine Avicel PH 105 Avicel PH 105 Avicel PH 105

– Aerosil Aerosil – Aerosil Aerosil – Aerosil Aerosil

17.49 0.29 18.18 0.38 18.32 0.18 32.3 0.42 31.43 0.36 32.45 1.04 18.5 0.37 17.57 0.25 18.24 0.04

21.7 22.11 22.55 38.92 38.32 39.33 21.38 20.91 21.06

200P R972 200P R972 200P R972

0.63 0.64 0.47 0.42 0.15 0.27 0.42 0.28 0.10


355

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) Avicel PH105; and Aerosil R972 coated powders, (c) corn starch, (f) lactochem fine, (i) Avicel PH105.

356


Table 3 Surface roughness of excipient pellets. Sample

Ra (nm)

Rrms(nm)

Starch uncoated Starch 200P Starch R972 Lactochem fine uncoated Lactochem fine 200P Lactochem fine R972 Avicel PH105 Uncoated Avicel PH105 200P Avicel PH105 R972

20.80 4.23 32.10 3.65 28.70 5.94 35.95 3.2 39.47 5.98 28.90 3.84 29.45 3.04 20.75 2.48 24.00 2.14

28.10 40.08 36.80 48.20 54.3 41.40 37.25 27.60 43.65

4.44 5.90 7.04 5.43 7.71 5.4 3.89 4.40 8.39

All the pellet surfaces exhibited almost comparable roughness values which were much below 100 nm. Since the average roughness values for all the pellets were very less, these surfaces can be considered to be practically smooth with respect to the reported surface roughness values that affect contact angle measurements (Ryan and Poduska, 2008; Zografi and Johnson, 1984). Results from AFM study thus eliminate the possibility of influence of surface roughness factor on contact angle measurement using sessile drop method. 3.3. Wettability of powders by sessile drop contact angle method

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

FESEM analysis of uncoated excipient powders revealed that corn starch particles have nearly spherical shape with smooth surface appearance (Fig. 1a). The lactochem particles were slightly cylindrical in shape with relatively smooth surface containing some associated fines (Fig. 1d). On the other hand, Avicel PH105 particles consisted of highly irregular shaped particles with rough surface (Fig. 1g). FESEM images of dry coated particle shows that the corn starch particles were more efficiently and uniformly coated (Fig. 1b and c) followed by lactochem particles (Fig. 1e and f) and least coating was achieved with Avicel PH105 particles (Fig. 1h and i). These observations were further confirmed from the surface energy studies, discussed in the later sections. Thus, it can be said that the extent of surface coating depends on the particle shape and surface texture. Corn starch particles being more uniformly shaped and with smoother surface were more efficiently coated with the nano-silica particles than Avicel PH105 particles which are irregular in shape and having rough surface texture. Also, from the images it was found that Aerosil R972 gave more efficient coating as compared to Aerosil 200P. 3.2. Surface roughness determination of the compacts The values for average surface roughness (Ra) and rms roughness (Rrms) of pellets used for contact angle experiments (goniometric method) were calculated from AFM study (Table 3).

Fig. 2 shows the image of the contact angle of glycerol drop placed on different excipient surfaces at the end of 1 s. In all cases, it was found that contact angle of the Aerosil 200P coated excipients is less than corresponding uncoated excipients. When compared with the measured contact angle of Aerosil R972 (hydrophobic) coated excipients and that of Aerosil 200P (hydrophilic) coated excipients, it was found that powders coated with 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 in Table 4. During the experiment with water as a test liquid, it was observed that drops placed on starch compacts were immediately taken up by the compacts and owing to the swelling behavior, the contact angle determination for corn starch using water was impossible. However, with glycerol as a test liquid which is more viscous and hence didn't penetrate into starch surface as quickly as water, Aerosil 200P (hydrophilic) coated starch compacts showed a significant decrease in the mean contact angle from 41.60 for uncoated compacts to 23.46 indicating increase in wettability of its surface. Whereas for Aerosil R972 (hydrophobic) coated compacts, the mean contact angle increased to 50.95 signifying increased hydrophobicity (lower wetting behavior) of the surface. The work of adhesion of glycerol with uncoated starch compacts increased from 111.88 mJ/m2 to 122.71 mJ/m2 for hydrophilic coating whereas it decreased to 104.4 mJ/m2 for hydrophobic type of nano-coating indicating more interaction between glycerol and hydrophilic nano-silica on the surface and increased wetting

Fig. 2. Images of glycerol drop placed on the excipient surface at the end of 1 s.


357

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

Corn starch Corn starch 200P coated Corn starch R972 coated Lactochem fine Lactochem fine 200P coated Lactochem fine R972 coated Avicel PH105 Avicel PH105 200P coated Avicel PH105 R972 coated

Mean contact angle ( )

Work of adhesion, Wa (mJ/m2)

Water

Glycerol

– – –

41.60 23.46 50.95 19.84 17.49 28.2 22.23 19.86 24.88

0.0 0.0 0.0 0.0 34.2 2.55 30.6 2.04 28.4 2.10 40.0 1.71

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

2.33 1.04 1.74 2.32 1.23 2.22 1.68 1.09 2.8

Water

Glycerol

– – –

111.88 122.71 104.44 124.16 125.03 120.37 123.22 124.19 122.02

145.6 145.6 132.98 140.18 136.82 128.52

0.0 0.0 1.82 0.99 1.30 1.45

1.23 0.37 0.89 0.84 0.42 1.15 0.68 0.41 1.33

respectively. The work of adhesion for uncoated and coated lactose compacts showed similar trend as observed with corn starch powders (Table 4). The changes in contact angle and work of adhesion for surface modified Avicel PH 105 powders were comparatively less prominent due to the poor quality of coating achieved (observed from FESEM studies). In general, with increase in hydrophilic nature of the surface, the contact angle values determined using polar test liquids (de-ionized water or glycerol) decreased and vice versa with hydrophobic coating. Also, in all cases the work of adhesion for water was higher than that of glycerol. This is because of higher surface tension of water than glycerol (Table 1, Eq. (3)). Overall, the results showed that nanocoating resulted in the modification of surface wettability characteristics and by controlling the nature of coating (hydrophilic or hydrophobic), wettability characteristics of the powders can be changed to the desirable extent. However, these changes were found to be dependent on the quality of coating achieved, which in turn appears to be strongly dependent on type of nanoparticle used for coating as well as on the morphology of host particles as described from FESEM results. 3.4. Wettability determination by liquid penetration method

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.

Wettability of excipients from liquid penetration experiments is shown in Fig. 3. It was observed that as the water penetrate through the powder bed, it gradually wets the particles. Fig. 3 depicts the square of mass gain of water as a function of time for all uncoated and coated powders. The plots of mass square vs. time showed a linear relation for all the powder samples which was followed by a saturation phase. However, variation in slope for different powder samples indicated difference in the liquid penetration rate which is dictated by the wettability characteristics of the particle surface. From Fig. 3a it can be seen that uncoated starch powder showed very slow water penetration rate but it was still greater than that observed for hydrophobic coated corn starch. On the other hand, starch coated with hydrophilic silica showed extremely high mass gain of water. Lactochem uncoated and those coated with hydrophilic silica powders found to have similar initial water uptake (upto 20 s). However, after that it remained constant for former (uncoated) reaching an almost equilibrium (Fig 3b). In case of Avicel powders, similar trend for water penetration was observed with hydrophobic and hydrophilic coating (Fig.3c). However, the difference in the slopes of curves was found to be less between Avicel PH105 uncoated and coated powders due to lower surface coverage of nano-coating. In general, higher penetration rates were observed for hydrophilic type of coating and vice versa for hydrophobic coating for all powders. This can be explained from the fact that during its penetration course through the powder bed, it encounters hydrophilic and hydrophobic

358


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

Starch Uncoated Starch 200P coated Starch R972 coated Lactochem uncoated Lactochem 200P coated Lactochem R972 coated Avicel PH105 uncoated Avicel PH105 200P coated Avicel PH105 R972 coated

Contact angle

Liquid penetration rate

Poured bulk density

Tapped bulk density

(g/s)

Material constant, C x 1014 (m5)

( ) 84.55 2.4 78.45 1.75 85.57 2.01 79.22 1.64 68.90 1.87 82.72 0.82 52.04 1.54 37.35 0.86 58.13 1.02

(g/ml)

(g/ml)

0.016 0.00 0.035 0.00 0.009 0.00 0.039 0.00 0.067 0.01 0.018 0.01 0.088 0.00 0.091 0.00 0.058 0.00

1.142 0.24 0.996 0.03 0.512 0.08 1.507 0.08 0.785 0.08 0.506 0.04 1.678 0.00 1.182 0.06 0.980 0.07

0.40 0.02 0.59 0.02 0.64 0.01 0.44 0.01 0.54 0.01 0.66 0.02 0.31 0.01 0.33 0.00 0.36 0.01

0.65 0.01 0.72 0.00 0.79 0.01 0.77 0.01 0.92 0.00 0.98 0.01 0.49 0.00 0.57 0.00 0.62 0.01

particle surface. For hydrophilic type of coating, water encounters majority of hydrophilic surface which increases the spreading of water within shorter duration of time. With hydrophobic type of coating, water encounters hydrophobic surface which decreases water spreading and slow penetration through the bed. From the liquid penetration profiles obtained for different powders, contact angle values for water as test liquid was calculated using modified Washburn equation (Eq. (2)). Table 5 presents the calculated contact angle values, penetration rates calculated from the slope linear portion of water absorption curve and material constant values along with the poured bulk and tapped bulk density obtained for uncoated and coated excipients. It can be observed that the material constant decreases after surface modification but the extent of decrease depends on the type of coating performed (Table 5). This can be attributed to the fact that it depends on the powder packing properties as described in Table 5. As Aerosil R972 coated powders are more closely packed (achieved more poured and tapped density), material constant for these excipients was found to be lowest followed by Aerosil 200P coating and highest for uncoated excipients. This variation in the materials constant can influence the water penetration rate and wettability characteristics of powder. 3.5. Comparison of wettability determination methods Comparison of contact angle values obtained from sessile drop method and Washburn method revealed a large difference in these data (refer Tables 4 and 5). For starch samples, as direct contact angle measurement using water was not possible hence for comparison purpose contact angle values using glycerol as test liquid were referred. The difference in contact angle data was found to be even greater for corn starch and lactochem powders where coating was comparatively good. For all powders, contact angle values obtained from liquid penetration method (advancing contact angle) were considerably higher than those obtained with sessile drop technique (static contact angle). This difference in contact angle from two methods is also widely reported in literature (Chibowski and Hołysz, 1997; Grundke and Augsburg, 2000). Also, it has been clearly reported in literature that contact angles obtained from Washburn method are usually an overestimation of those obtained from sessile drop method for the same solids (Chibowski and Perea-Carpio, 2002). These differences observed was due to difference in measurement techniques. However, in spite of difference in absolute values of the contact angle, the wettability trend remained similar in both the cases. Hydrophilic coating resulted decrease in contact angle (higher wetting behavior) and hydrophobic coating resulted increase in contact angle (lower wetting behavior) with respect to the corresponding values for uncoated powders. As the contact angle from liquid penetration method is affected by the factors such as particle morphology, bed porosity and

sample preparation method, most of the time the contact angle data from Washburn equation underestimates the surface energies of the solids (Chibowski and Perea-Carpio, 2002). Hence, static contact angle values from sessile drop technique with glycerol as test 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 the excipient powders. A general trend of slight decrease in dispersive surface energy (g sd) and increase in polar surface energy (g sp) was observed for Aerosil 200P coated powders. While decrease in g sd can be attributed to the passivation of high energy sites (Han et al., 2013), the increase in g sp can be explained from the hydrophilic nature of nano-particles which has hydroxyl groups on its surface (Rudiger, 2009). In case of coated starch powder (Fig. 4a), although g sd decreased slightly from 45.13 mJ/m2 to 43.89 mJ/m2, there was a significant increase of the polar surface energy from around 9 mJ/ m2 for uncoated corn starch to 18 mJ/m2 for hydrophilic coating resulting in an overall increase in total surface energy from 54.5 mJ/m2 to 62.47 mJ/m2 (Fig. 4a). This is mainly because the hydroxyl groups present on Aerosil 200P interacts more with the polar solvents causing increase in g sp and consequent reduction in contact angles (discussed earlier). For Aerosil 200P coated lactochem powder, a marginal decrease in g sd from 46.43 mJ/m2 to 45.99 mJ/m2 was observed whereas gsp increased from 16.70 mJ/ m2 to 19.34 mJ/m2. In case of Aerosil 200P coated Avicel powders, both g sd and g sp 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 is because the hydrophobic coating resulted in decrease in the dispersive (g sd) as well as polar components (g sp) of surface energy for all the powders. A significant decrease in polar surface energy (g sp) component for Aerosil R972 coated powders were observed with an exception of Aerosil R972 coated Avicel PH105 (Fig. 4b) due to poor quality of the coating. The g sp decreased from 9.37 mJ/m2 to 6.10 mJ/m2 and 16.70 mJ/m2 to 14.21 mJ/m2 for corn starch and lactochem powders respectively. This decrease in the polar components can be explained from the fact that, hydrophobic silica is synthesized by treatment of hydrophilic silica with di-methyl di-chlorosilane which results hydrophobic alkyl chains on surface of hydrophilic silica particle (Rudiger, 2009). This reduces the interaction of surface with the polar liquids and the surface became comparatively less wetting which is reflected in contact angle values with Aerosil R972 coated powders as indicated in Table 4. Wettability of powders was also quantified using spreading of a liquid over a solid surface called as spreading co-efficient (Rowe, 1989). Spreading coefficient of water and glycerol for excipient


359

Fig. 4. Polar, dispersive and total surface energies for (a) corn starch, (b) lactochem fine 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.

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

obtained with water as a test liquid since glycerol has lower surface tension as compared to water (refer Table 1). This was also evident in work of adhesion data evaluated from contact angle data in Table 4. 3.7. Surface energy determination from Inverse gas chromatography Fig. 6 depicts the dispersive, polar and total surface energies for uncoated and surface modified excipient powders at an infinite dilution of 3% probe surface coverage. Results showed that all the

360


nano-coated powders exhibited a general trend of decrease in the g sd values and alteration in g sp component based on the nature of nano-silica i.e., hydrophilic or hydrophobic. With Aerosil 200P coating the g sd decreased from 48.03 mJ/m2 to 40.09 mJ/m2 for starch, 47.95 mJ/m2–41.65 mJ/m2 for lactochem and 47.17 mJ/m2–43.96 mJ/m2 for Avicel PH 105. On the other hand, the g sp 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 for Avicel PH105. Thus, hydrophilic coating led to increase in g sp values for all excipients and decrease in g sd.

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 dispersive components of surface energy of all excipients as observed with Aerosil 200P coated powder. The g sd decreased to 37.5 mJ/m2and 36.75 mJ/m2for starch and lactochem respectively as compared to g sd of these uncoated powders (mentioned above). For Avicel PH 105, the g sd found to decrease from 47.17 mJ/m2 to 43.86 mJ/m2. The gsp values for starch and Avicel PH105 showed very little decrease with respect to lactochem coated powders which showed decrease from 8.9 mJ/m2 to 3.85 mJ/m2. Thus, Aerosil R972 was found to be more effective in reducing the dispersive component of surface energy whereas Aerosil 200P was found to be more effective in increasing the polar surface energy of all excipients. These observations are consistent with the surface energy calculated form sessile drop experiments in terms of their trends observed with different types of coatings. Overall, for the same nano-particle, the quality of nano-coating varied depending on the type of the excipients and their surface morphology which was further reflected in the surface energy results obtained for different powders. 3.8. Comparison of surface energy determination from contact angle and IGC methods

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

Comparison of the surface energy values calculated from contact angle data and IGC approach for uncoated and coated powders revealed that values obtained from both the methods followed similar rank order. Consistent to the previous studies given in literature, not much difference in g sd values were observed from two different methods (Dove et al., 1996). However, it should be noted that IGC results showed greater decrease in g sd values as compared to the values obtained from contact angle approach for both Aerosil 200P and Aerosil R972 coating. Interestingly, in most of the cases g sp values obtained from contact angle approach were considerably higher than those obtained from IGC studies. These differences in the magnitude of surface energy components of uncoated and coated powders can be due to difference in the nature and treatment of the test samples under study and also due to difference in the theoretical approaches used for surface energy calculation. In contact angle method, powders were compressed to form compacts whereas the powder samples required no treatment for IGC experiments. Also, it can be said that the contact angle approach provides the surface


361

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

energy information which is averaged over a larger surface area (at macroscopic level) as the liquid spreads and interacts over solid surface, whereas surface energy determination using IGC at infinite dilution provides information from only limited but significantly active sites on the surface. Overall, both the techniques used for surface energy determination of solids were able to gauge similar type of changes in surface energetics of powders before and after surface modification. 3.9. Wettability and polar surface energy As polar surface energy plays a crucial role towards surface wetting of a solid, polar component of surface energy obtained from IGC results was correlated to the contact angles using sessile drop technique. Fig. 7 shows the contact angle obtained with glycerol as test liquid for all excipients as a function of polar surface energy (g sp) determined from IGC experiments. As expected, with increase in g sp contact angle decreased for all excipients. From the results obtained, uncoated lactochem fine powder was found to have highest polar surface energy followed by corn starch and least polar surface energy for Avicel PH105. The variations in contact angle values after nano-coating were most prominent for coated corn starch and lactochem fine powders where quality of the coating was comparatively better. The lowest variation was observed with Avicel PH105 powders due to low level of coating

achieved. The plot shows that Aerosil 200P coated powders mostly occupy the lower-right bottom region of the plot whereas the Aerosil R972 coated powders moves towards the upper-left region of the plot indicating enhancement and reduction of wetting behavior respectively based on the nature of coating. This is because of hydrophilic type of coating with Aerosil 200P consisting of higher polar functional groups led to increase in g sp of the excipients which in turn reduced the contact angle. These results suggest that the polar component of surface energy can be inversely correlated to the contact angle values i.e., higher g sp relates to lower contact angle. 3.10. Contact angle and surface energy as a function of level of nanocoating FESEM images for starch powders with different level of Aerosil R972 coating are shown in the Fig. 8. It can be seen from the images that the 0.25% w/w coating was less dense than that of the coating observed at 0.5% w/w and 1.0% w/w levels. Surface area coverage calculated through image processing confirmed the observations from FESEM study. For 0.25% w/w nano-coating level, the surface area coverage was found to be on the lower side of about 18.5%. On the other hand, the surface area coverage for 0.5% w/w and 1.0% w/w levels were found to be in the similar range of around 53% and 57%, respectively.

362


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

Fig. 9a and b depicts the work of adhesion (Wa) as a function of surface coverage of nano-coating with hydrophobic silica on corn starch particles. It can be seen that, with the increase in % of surface coating, Wa decreased gradually indicating incremental nonwetting behavior due to increased hydrophobicity of the surface. From Fig. 9 it can be observed that at higher levels of surface coverage (above 50%) Wa was found to be sensitive to a very small 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% to 57% 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). This indicates that even a small change in the particle surface can significantly affect its wetting properties at higher level of surface coating. Fig. 9a and b shows the changes in polar and dispersive surface energies as a function surface coverage. The polar as well as the dispersive 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 respectively as the coating level increased from 0% w/w to 1% w/w. The progressive decrease in dispersive surface energies is because at higher coating levels, plugging of the high energy sites on particle surfaces will occur and thus the non-polar and polar probes can now interact either with the nano-silica which has lower dispersive component (Chen et al., 2010) or with other lower energy sites on the starch particle resulting in the decrease in the overall dispersive and polar components of surface energy. This indicates that the different nano-coating levels used here, ranging from 0.25% w/w to 1% w/w, did influence the overall surface energy and contact angle values. Hence, based on the nature and level of surface coverage, desired surface wetting and energetic can be achieved. 4. Conclusion The present work describes the influence of surface modification using nano-coating on surface characteristics of three pharmaceutical excipient powders viz. Avicel PH 105, lactochem fine powder and corn starch. Dry coating of excipients was performed using hydrophilic (Aerosil 200P) and hydrophobic

(Aerosil R972) colloidal silicon-di-oxide as guest particle. The wetting behavior of powder surface was assessed from both static and advancing contact angle measurements using sessile drop method and liquid penetration (Washburn method) method respectively. The polar (g sp) and dispersive (g sd) components of surface energies were determined from extended Fowke's equation using static contact angle data and inverse gas chromatography (IGC) technique at infinite dilution. The results showed that Washburn method provided comparatively higher contact angle values as compared to the sessile drop technique for the same samples. However, both these techniques were able to differentiate successfully the changes in hydrophilicity and hydrophobicity of surfaces with the nature of nano-particles used for coating. Wettability assessed in terms of spreading co-efficient of polar liquids on excipient surfaces indicated that Aerosil 200P facilitated spreading of liquids due to increased polarity of the surface. This resulted in higher work of adhesion and greater spreading co-efficient. In contrast, Aerosil R972 coating prevented spreading which was reflected by reduced value of spreading coefficient and work of adhesion. Analysis of surface energy values showed a general trend of decrease in dispersive surface energy for all the surface modified powders due to passivation of most active sites on the surface. However, depending on the nature of the functional groups present in nano-silica, g sp was found to be higher or lower for hydrophilic and hydrophobic coating respectively. Results also showed that wettability increase with increasing the polar component of the surface energy. Both the techniques for surface energy determination provided comparable and similar trends in g sp and g sd components of surface energies for uncoated and nano-coated excipients. g sd values from sessile drop and IGC methods were found in the similar range. However, calculated g sp values from contact angle approach showed comparatively higher variations than corresponding measured value of g sp from IGC. The study also successfully demonstrated that surface wettability and energetics of powders can be modified by varying the level of surface coating for various process requirements in pharmaceutical or other powder operations. Acknowledgements We acknowledge IITGN for financial support for this work and Evonik Degussa Industries for providing nano-silica as a gift sample for this research. We would also like to acknowledge Manish Thakkar from Shah Schulman Centre for Surface Science and Nanotechnology for helping with the contact angle experiments. References Buckton, G., Beezer, A.E., 1988. A microcalorimetric study of powder surface energetics. Int. J. Pharm. 41, 139–145. Buckton, G., Choularton, A., Beezer, A.E., Chatham, S.M., 1988. The effect of the comminution 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 drug delivery 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 and bulk 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 angle determination. J. Adhes. Sci. Technol. 11, 1289–1301. Chibowski, E., Perea-Carpio, R., 2002. Problems of contact angle and solid surface free 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 and total surface energy distributions of particulates by inverse gas chromatography. Langmuir 27, 521–523. Dove, J.W., Buckton, G., Doherty, C., 1996. A comparison of two contact angle measurement methods and inverse gas chromatography to assess the surface energies of theophylline and caffeine. Int. J. Pharm. 138, 199–206.

V. Karde, C. Ghoroi / International Journal of Pharmaceutics 475 (2014) 351–363 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 binary powdered systems: an application of surface heterogeneity profiles to understanding 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-faceted characterization of pharmaceutical powders to discern the influence of surface modification. Powder Technol. 236, 63–74. Ghoroi, C., Han, X., To, D., Jallo, L., Gurumurthy, L., Davé, R.N., 2013b. Dispersion of fine 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 of porous polymer materials. J. Adhes. Sci. Technol. 14, 765–775. Han, X., Ghoroi, C., To, D., Chen, Y., Davé, R., 2011. Simultaneous micronization and surface 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 for improved 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-energy sites of milled ibuprofen crystals via dry coating for reduced cohesion and improved flowability. J. Pharm. Sci. 102, 2282–2296. Heng, J.Y.Y., Thielmann, F., Williams, D.R., 2006. The effects of milling on the surface properties 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 flow and 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 surface characterisation and comparison of two potential sub-micron sugar bulking excipients for use in low-dose, suspension formulations in metered dose inhalers. Int. J. Pharm. 361, 209–221. Lefebvre, G., Galet, L., Chamayou, A., 2011. Dry coating of talc particles: effect of material 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 by surfactant solutions. Int. J. Pharm. 128, 29–44. Mujumdar, A., Wei, D., Dave, R.N., Pfeffer, R., Wu, C.-Y., 2004. Improvement of humidity resistance of magnesium powder using dry particle coating. Powder Technol. 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 comil for 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 of inverse 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 for Solvent-Free Epoxy Resins. Evonic.

363

Ouabbas, Y., Dodds, J., Galet, L., Chamayou, A., Baron, M., 2009. Particle–particle coating 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 of powder wettability. Int. J. Pharm. 152, 1–5. Pfeffer, R., Dave, R.N., Wei, D., Ramlakhan, M., 2001. Synthesis of engineered particulates 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 free energy of powders assessed using inverse gas chromatography and contact angle measurements. Int. J. Pharm. 221, 211–217. Puri, V., Dantuluri, A.K., Kumar, M., Karar, N., Bansal, A.K., 2010. Wettability and surface chemistry of crystalline and amorphous forms of a poorly water soluble drug. Eur. J. Pharm. Sci. 40, 84–93. Ramlakhan, M., Wu, C.Y., Watano, S., Dave, R.N., Pfeffer, R., 2000. Dry particle coating using magnetically assisted impaction coating: modification of surface properties and optimization of system and operating parameters. Powder Technol. 112, 137–148. Rowe, R.C., 1989. Polar/non-polar interactions in the granulation of organic substrates 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 dynamic contact 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 for thermodynamic 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 poorly water-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. Wettability measurement apparatus for porous material using the modified Washburn method. 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 and thin 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 a mechanical 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.

Wettability of pharmaceutical solids: estimates of solid surface polarity.

Theoretical model of droplet wettability on a low-surface-energy solid under the influence of gravity.

Influence of lipid coatings on surface wettability characteristics of silicone hydrogels.

Decoupling the contribution of dispersive and acid-base components of surface energy on the cohesion of pharmaceutical powders.

Laser surface modification of AZ31B Mg alloy for bio-wettability.

Titanium surface characteristics, including topography and wettability, alter macrophage activation.

Influence of PEEK surface modification on surface properties and bond strength to veneering resin composites.

Effect of crystal habits on the surface energy and cohesion of crystalline powders.

Influence of surface treatment of contaminated zirconia on surface free energy and resin cement bonding.

The influence of fabric surface characteristics on satellite bloodstain morphology.

Role of Titanium Surface Topography and Surface Wettability on Focal Adhesion Kinase Mediated Signaling in Fibroblasts.

Potential role of surface wettability on the long-term stability of dentin bonds after surface biomodification.

Particle engineering in pharmaceutical solids processing: surface energy considerations.

Effects of surface wettability on gecko adhesion underwater.

Evaluation of wettability and surface energy of native Nitinol surfaces in relation to hemocompatibility.

Selective Area Modification of Silicon Surface Wettability by Pulsed UV Laser Irradiation in Liquid Environment.

Surface Wettability Modification of Cyclic Olefin Polymer by Direct Femtosecond Laser Irradiation.

Altering Emulsion Stability with Heterogeneous Surface Wettability.

Surface Modification and Damage of MeV-Energy Heavy Ion Irradiation on Gold Nanowires.

Redox-Induced Backbiting of Surface-Tethered Alkylsulfonate Amphiphiles: Reversible Switching of Surface Wettability and Adherence.

Actuating Water Droplets on Graphene via Surface Wettability Gradients.

Influence of Surface Modification on the Microstructure and Thermo-Mechanical Properties of Bamboo Fibers.

Influence of water content in mixed solvent on surface morphology, wettability, and photoconductivity of ZnO thin films.

The influence of surface free energy and surface roughness on early plaque formation. An in vivo study in man.