G Model IJP 14931 No. of Pages 13

International Journal of Pharmaceutics xxx (2015) xxx–xxx

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

Roller compactor: The effect of mechanical properties of primary particles Riyadh B. Al-Asady, James D. Osborne, Michael J. Hounslow, Agba D. Salman* Department of Chemical and Biological Engineering, University of Sheffield, Mappin Street, Sheffield, S1 3JD, UK

A R T I C L E I N F O

A B S T R A C T

Article history: Received 13 February 2015 Received in revised form 17 May 2015 Accepted 23 May 2015 Available online xxx

In this study, the nano-indentation hardness of a single primary particle was measured for six different materials; microcrystalline cellulose, hydroxypropyl methylcellulose, maltodextrin, lactose, sodium carbonate and calcium carbonate. This was linked to the properties of the ribbons produced by roller compactor at different hydraulic pressures in the range of 30–230 bar. The main investigated ribbon properties were strength, porosity and width. For the range of materials that were tested, it was found that the lower the nano-indentation hardness of the powder particles, the higher the strength, width and lower the ribbon porosity. This is because the applied pressure by the rollers was enough to plastically deform the particles and create bonds between them. A method was suggested to predict the workability of the powder in roller compactor by using the data of nano-indentation for three materials. ã2015 Elsevier B.V. All rights reserved.

Keywords: Roller compactor Nano-indentation hardness Yield strength Ribbon properties

1. Introduction A roller compactor consists of two rotating rollers which apply high pressure to powder particles to agglomerate them together and produce ribbon so the bonding of the particles depends largely on the compressibility of the material (Guigon et al., 2007). The ribbons can be used as a final product but in many industries, including pharmaceutical industry, the ribbon is milled to produce granules that flow easily (Guigon et al., 2007). The strength and porosity of the ribbons are considered to be the most important properties (Lim et al., 2011; Miguélez-Morán et al., 2009; Tye et al., 2005; Wu et al., 2006) since both of them affect the properties of granules (size distribution) produced from the milling of the ribbons. The granule size distribution is important since it influences the properties and behavior of granules (Litster and Ennis, 2004). The properties of the primary particles and the process parameters of the equipment play an important role in controlling ribbon and granules properties (Guigon et al., 2007). In term of the properties of the primary powders, previous studies showed that the primary particle size and moisture content have significant effect on the quality of the roller compactor ribbon and granules. Inghelbrecht and Paul Remon

* Corresponding author. Tel.: +44114 2227560 E-mail addresses: riyadh.bakir@sheffield.ac.uk (R.B. Al-Asady), a.d.salman@sheffield.ac.uk (A.D. Salman).

(1998) stated that small size powder showed good binding property and the opposite for large particle size. These results confirmed by Herting and Kleinebudde (2007) which showed that the median granule size resulted from crushing of the ribbon increased with decrease in the primary particle size. To investigate the effect of the moisture content of primary powder, a study conducted by Gupta et al. (2005) stated that increasing the moisture content of the microcrystalline cellulose powder assists the particle rearrangement and plastic deformation process because the yield strength decreases with increasing the moisture content. Another study by Wu et al., (2010) showed that increasing the moisture content of the primary powder undergoing roller compaction between fixed gap rollers caused increase in the applied pressure to the powder because the powder do not flow easily due to cohesiveness which caused increase in the mass of the powder between the two rollers. It is worth mentioning that the powder was fed into compaction zone by gravity so flowability of the material plays an important role and this effect is related to the equipment. Osborne et al. (2013) revealed that increasing the moisture content of the amorphous material caused an increase in the ribbon tensile strength and decrease in the porosity. Roller compactor was used to produce ribbons and granules of different materials. Microcrystalline cellulose (MCC) is the most used excipient for roller compaction due to its excellent compressibility (Chang et al., 2008; Inghelbrecht and Remon, 1998). Previous studies showed that microcrystalline cellulose is a

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plastically deformable material, so a wide range of parameter settings of roller compactor, such as roller speed and pressure, can be used to produce good ribbon and granules (Inghelbrecht and Remon, 1998; Falzone et al., 1992). Addition of ibuprofen to the MCC powder caused decrease in its binding ability (Inghelbrecht and Remon, 1998). Another study conducted by Yu et al. (2012), stated that MCC produced regular shape ribbons with high strength since it is compressible material. According to Bultmann (2002), MCC is used not only as filler but also as a binder for compaction process due to its excellent plastic deformability. The compressibility of MCC decreased with multicompaction due to the work of hardening so the binding ability is decreased as well (Bultmann, 2002; Kleinebudde, 2004). Lactose produced ribbons with different properties depending on the process parameters and the type of lactose powder (Inghelbrecht and Paul Remon, 1998). Calcium carbonate powder has a low compressibility and therefore, produced weak ribbons when it was compacted alone (Bacher et al., 2007). During compaction-granulation, the particles of the powder are subjected to a certain load depends on the piece of equipment and process parameters. There are four types of possible response of material upon applying and increasing the load to the powder particles. These are particle rearrangement and interlocking, reversible elastic deformation, permanent plastic deformation and fracture (Khossravi and Morehead, 1997). The interlocking and plastic deformation is both responsible for the strength of the ribbon. The interlocking is expected to be significant at low pressure (Farber et al., 2008). The plastic deformation of the material can be evaluated by measuring the hardness. There are three scales to measure the hardness which are macro, micro and nano. Macro and micro scale apply relatively high force by relatively big indenter so the measurement may be affected by the bonding strength between the particles. Example of this type is Vickers’s hardness. Microindentation has been used previously to indent the surface of the ribbon in order to measure the density distribution across the width of the ribbon (Miguélez-Morán et al., 2009). For the nano scale hardness measurement and comparing to the micro scale (Oliver and Pharr, 1992), the indenter is smaller with lower applied force, which could be of an order of 1 nN (Askeland, 1998; Broz et al., 2006). The aim of this study is to investigate the link between the properties of the ribbon of different materials produced by roller compactor with the mechanical properties of a single primary particle measured by nano-indentation technique. This link is especially important when the material is expensive or not available in large quantities. This is the case with new pharmaceutical products (Perkins et al., 2007). An approach was suggested to predict the workability of the powder during the roller compaction process by comparing their mechanical properties with applied pressure on the material.

Fig. 1. Typical force displacement curve for nano-indentation hardness.

hc ¼ hmax  Q

F max S

(2)

hmax the maximum depth of penetration in nm, Q constant which depends on indenter shape (for Berkovich indenter = 0.75), S unloading stiffness (nN/nm) of material and can be calculated from the unloading curve data in Fig. 1 and Eq. (3): S¼

dF dh

(3)

2. Nano-indentation hardness Fig. 1 shows the typical force displacement data resulted from the nano indentation measurement. By using force displacement data, shown in Fig. 1, The nano-indentation hardness can be calculated using Eq. (1) (Oliver and Pharr, 1992). H¼

F max Ap ðhc Þ

(1)

H nano-indentation hardness in GPa, Fmax maximum force in nN as indicated in Fig. 1, Ap(hc) projected contact area in nm2, hc indenter’s contact depth with the tested sample at Fmax in nm and can be calculated by using Eq. (2): Fig. 2. Schematic diagram of roller compactor.

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3. Yield strength of the material The yield strength (Py) of the material is the stress at which the material starts to deform plastically. Before this point, the material deform elastically so it will return to it is original shape after removing the load. Yield strength of the material can be determined from measuring its hardness. Tabor (1951) proposed to divide the hardness by approximately three to get the yield strength. This relation is used widely for different materials in spite of its limitations (Lee et al., 2008). To calculate the yield strength from force displacement curve, the elastic region should be specified. Hertz equation (Johnson, 1985; Mangwandi et al., 2015, 2007; Thornton, 1997) describes the relation between the applied force and the resulted displacement for a sphere particle and as follows: pffiffiffi 2  3=2 rE h (4) F¼ 3 F applied force in nN, r radius of the maximum possible contact area between the indenter and the particle in nm, E reduced effective young modulus in GPa, h displacement in nm. This equation fits the elastic region of the force displacement curve. For stress greater than elastic limit, the particle deform plastically and the force displacement data can be described by the following equation (Thornton, 1997) dF ¼ prPy dh

(5)

dF/dh slope of the force displacement in the plastic region, Py yield strength in GPa. 4. Stress in roller compactor The first model that described the behavior of the powder between the rollers was created by Johanson (1965); Guigon et al., 2007). By applying Johanson’s model, the maximum normal stress applied to the powder can be calculated taking into consideration material properties, roller geometry and process parameters. This is the main advantage of Johanson’s model, it needs a few powder properties to determine the nip angle and the maximum applied normal stress. Johanson’s model was originally based on Jenike yield criteria for hoppers and silos. Bindhumadhavan et al. (2005) used transducer fitted to the roller to measure the pressure profile normal to the roller surface and compare the results with the pressure profile calculated by Johanson’s theory. They found that Johanson’s theory were able to predict the pressure profile along roller surface. In this study Johanson’s theory was used to calculate the maximum applied normal stress on the powder between the rollers. The roller compaction process is usually thought of as having three different regions by which the powder passes through. These are known as the slip, nip and release regions and are shown in Fig. 2. For the plane strain condition between the rollers, the effective yield function can be represented as shown in Fig. 3. Johanson, (1965) presented that the pressure gradient in the slip region can be calculated by the following equation:     4su p ds 2  u  n tandE  ¼ D (6) dx slip 2 1 þ Ds  cosu cotðA  mÞ  cotðA þ mÞ

su is the mean normal stress at position u, u is the angular position in roll bite,dE is the effective angle of the internal friction (related to material flow property), D is the roll diameter, s is the gap between the roll, A is parameter given by A ¼ u þ v þ p2 =2,n is acute angle

Fig. 3. Jenike-shield yield criterion (Bindhumadhavan et al., 2005).

between the tangent to the roll surface and the direction of the major principal stress (s 1 ) and it is given by:   1 sinfw n ¼ p  sin1  fw (7) 2 sins u

fw is the angle of wall friction (related to material flow property), and m can be calculated by the following equation: m ¼ p=4  s u =2. The pressure gradient in the nip region is given by the following equation:   ds K s ð2cosu  1  s=DÞtanu   ¼ Du (8) s dx Nip 2 1 þ =D  cosu cosu where K is the compressibility factor determined by the following equation. log

p1 r ¼ Klog 1 p2 r2

(9)

p is the pressure in Pascal (p1 and p2 refer to the two values of pressure), r is the bulk density of the powder in kg/m3 (r1 and r2 refer to the bulk density of the powder after applying pressure of p1 and p2 respectively). Johanson suggests that the pressure gradients in the slip and nip angle are equal at the nip angle so the nip angle can be calculated by the following equation:

Table 1 The relation between hydraulic pressure and roll force (Alexanderwerk). Pressure (bar)

Roll force (KN)

20 40 60 80 100 120 140 160 180 200 215 230

8.29 16.59 24.88 33.17 41.47 49.76 58.05 66.35 74.64 82.94 89.16 95.38

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Table 2 True density of the powders as supplied by manufacturers.

pmax ¼

Material

True density (kg/m3)

Avicel PH-101 Tylopur 604 Glucidex1 6 Pharmatose 200M Light sodium carbonate Calcium carbonate

1561 1285 1440 1540 2533 2930

2Rf WDf

where Rf is the roll force in Newton (supplied by the manufacturer of roller compactor, Alexanderwerk). Table 1 shows the relationship between hydraulic pressure and roll force of the roller which depend on the equipment design, W is the width of the roller, f is the force factor which given by the following equation: uZ¼a"



ds dx



 ¼ slip

ds dx



f ¼ (10)

Nip

(11)

u¼0

#K s =D   cosudu 1 þ s =D  cosu cosu

(12)

Then the maximum stress applied on the powder (pmax) between the two rollers can be calculated using the following equation:

Fig. 4. SEM of the primary particles of different materials.

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logarithmic plot of the pressure versus bulk density and according to Eq. (9). The compression speed was 1 mm/min. Table 3 shows the measured flow properties of three materials.

5. Materials and methods 5.1. Materials Six different materials were used in this study; microcrystalline cellulose (Avicel PH-101) supplied by FMC Biopolymer (Ireland), hydroxypropyl methylcellulose (Tylopur 604) supplied by ShinEtsu (Japan), Malto dextrin (Glucidex1 6) supplied by Roquette (France), a-lactose monohydrate (Pharmatose 200 M) supplied by Dmv-Fonterra Excipients (Netherland), light sodium carbonate supplied by Brunner Mond, UK and calcium carbonate supplied by Longcliffe Quarries Ltd., UK. 5.2. Powder characterisation 5.2.1. Nano-indentation Nano-indentation equipment, Triboscope (TS70) manufactured by Hysitron Inc. (USA), combined with atomic force microscope (Dimension TM 3100, Veeco) was used to indent the samples using the standard Berkovich tip of three sided pyramid shape. To measure the hardness of a single particle, particles were spread and glued on a sample holder using resin and hardener (Araldite, Bosik Findly Ltd., UK). This has been chosen due to a setting time of 90 min which was a suitable time to spread the particles and remove some extra particles from under the optical microscope. The nano-indenter was calibrated using fused silica of known hardness which is considered a standard material to calibrate the nano-indenter. The calibration was carried out by using a load and penetration depth close to that expected to be applied to the material particles. At least five indentation cycles were carried out for each material. The load of approximately 200 mN was applied at a rate of 40 mN per second for five seconds and held for another five seconds, then unloaded for five seconds. 5.2.2. Size and true density of the primary powders The powder of each material was sieved using a sieve shaker (Retsch Technology, Germany) to sieve size between 63–212 mm. Table 2 shows the true density of the powders as supplied from the manufacturers. Fig. 4 shows the scanning electron microscope images of a single particle of six materials. 5.2.3. Flow properties and compressibility factor of the primary powder Peschl shear cell (Peschl and Colijin, 1977) test used to measure the effective angle of internal friction (dE) and angle of wall friction (fw) for three powders, Avicel PH-101, Pharmatose 200 M and calcium carbonate. The test principle is measuring the rotational shear stress under different normal stress and the angle of wall friction is measured against stainless steel plate. All the measurements were made under five different consolidation loads and at temperature of 25  C and 40% RH. The compressibility factor (K) was determined by compacting a sample with a pressure range of 12–250 MPa in a die of 10 mm inner diameter by using material testing machine (Instron 3367). The bulk density of the compact was measured for each pressure and the compressibility factor (K) was determined from the

5.3. Ribbon production and characterisation Pre to ribbon production, the powders were conditioned in humidity chamber (Binder KMF 240 climatic chamber, Binder, UK) and equilibrated at 40% relative humidity and 20  C for three days. The conditioned powder of each material was compacted using the Alexanderwerk WP 120 V Roller compactor (Alexanderwerk, Germany) with hydraulic pressure of 30, 70, 100, 150, 200 and 230 bar. The roller speed and roller gap were kept constant at 3 rpm and 3 mm respectively. The Alexanderwerk WP 120 V has a feed hopper that feeds the powder downwards towards the screw feeder which consists of one rotating screw with an adjustable speed. The horizontal screw feeder is used to transport, pre-compact and feed the material to the rollers. There is also a vacuum de-aerating system which removes the air from the feed screw system in order to improve the transportation of materials. The material then enters the gap area between two compaction rotating rollers. The rollers of knurled surface of 12 cm diameter and 4 cm width each are the main part of the equipment which are arranged vertically to each other and press the powder using controlled hydraulic pressure between 30 bar and 230 bar. There are two fitted cheek plates on both sides of rollers which prevent powder from the leaking from rollers. The roller gap value is controlled by an automated feedback system which keeps the gap size constant to the required value by automatically changing the feeder screw speed which changes the feed rate. The samples were collected at each set of conditions after achieving steady state for required parameters; hydraulic pressure and gap between the rollers. 5.3.1. Measurement of ribbon tensile strength A material testing machine BDO-FB, 0.5 TS, Zwick/ Roell, Germany, was used to measure the force required to break the ribbon and then to calculate ribbon tensile strength by using a three point test. The ribbon was placed on two supports, force was then applied to the centre of the ribbon at speed of 1 mm/min, and this force increased gradually until the ribbon broke. The measurement was repeated at least five times for each ribbon sample. By using the force required to break the ribbon in Eq. (13) the tensile flexural strength was calculated (Harirtian and Michael, 2000; Osborne et al., 2013).

sf ¼

3PL 2bw2

(13)

s f flexural strength in MPa, P force required to break the ribbon in N, L length between the two supports in mm, b width of the ribbon in mm, w thickness of the ribbon in mm. In order to follow the British standard (Institiution, 1977), the length between two supports always kept as calculated by Eq. (14): L ¼ ð16  1Þb

(14)

Table 3 Flow properties and compressibility factor of the primary powder of three materials. Material

Effective angle of internal friction (dE)

Angle of wall friction (fw)

Compressibility factor (K)

Avicel PH-101 Pharmatose 200 M Calcium carbonate

36.4 39.3 35.1

27.2 31 26.0

3 14.8 15.4

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Table 4 Measured hardness (H) for six different materials. Material

H (GPa)

Avicel PH-101 Glucidex16 Tylopur 604 Pharmatose 200M Light sodium carbonate Calcium carbonate

0.44 0.58 0.7 1.00 1.7 2.55

     

0.09 0.08 0.04 0.12 0.14 0.09

5.3.2. Measurement of ribbon porosity The bulk porosity of the ribbon was calculated by using Eq. (15):   rRibbon (15) ¼1

rtrue

Force (μN)

e bulk porosity of the sample, rRibbon ribbon bulk density in g/cm3, rtrue powder true density in g/cm3.

200 180 160 140 120 100 80 60 40 20 0 20

40

60

80

100

120

Displacment (nm)

Force (μN)

6. Results and discussion 6.1. Nano-indentation Different loads were initially tested to indent the particles of different materials. It was found that 200 mN load was a suitable load. Low load resulted in inconsistency of the results which agreed with previous work (Taylor et al., 2004) which could be because of a tip vibration that happens close to the surface which prevent a solid contact between the tip and the particle surface. The steady contact is important to obtain an accurate measurement and make the analysis of force-displacement curve easy (Taylor et al., 2004). On other hand, high load may cause cracks in the particles which will give an incorrect value for the hardness. Table 4 shows the measured values for hardness (H) as calculated by Eq. (1). Avicel PH-101 has the lower hardness which means it is the most plastically deformable material and the higher hardness was for calcium carbonate. 6.2. Yield strength of the material

0

200 180 160 140 120 100 80 60 40 20 0

As described in Section 3, the yield strength of the materials was determined using the force displacement data resulted from nano indentation experiment. Fig. 5 shows example of force displacement curves for three powders; Avicel PH-101, Pharmatose 200 M and calcium carbonate. The elastic limits were determined by plotting F2 versus h3 of the loading data and as shown in Fig. 6. The point of deviation from linear gradient is the end point of the elastic region. For the stress greater than the elastic limit the particle deform plastically and the force displacement data will be linear in this region and described by the Eq. (5) and as shown in Fig. 7. Table 5 shows the results of calculated yield strength for three different materials. 6.3. Ribbon production

0

20

40

60

80

100

120

100

120

Displacment (nm)

Force (μN)

The weight of the ribbon was measured by a 4 digits scale and the volume was measured by immersing the piece of ribbon in kerosene of a known volume (Litster and Ennis, 2004).

200 180 160 140 120 100 80 60 40 20 0 0

20

40

60

80

Displacment (nm) Fig. 5. Example of force-displacement data resulted from the nano indentation experiment ( CaCO3, pharmatose 200 M, Avicel PH-101).

As mentioned previously in Section 5.3, hydraulic pressures of 30, 70, 100, 150, 200 and 230 bar were used to produce ribbons of six different materials. However, there were no ribbons produced with calcium carbonate at 30 bar which suggests that the applied pressure was not enough to plastically deform the particles and cause them to bond together. There were no good size ribbon of sodium carbonate to measure the tensile strength at 30 and 70 bar. The ribbons produced by Pharmatose 200 M at 150 and 200 bar were not suitable for analysis since they split into two longitudinal parts. This could be due to the partial plasticity of Pharmatose 200 M which means that the materials of the inside layers of the ribbon need to recover after removing the stress, whereas the materials on the surface were plastically deformed. This failure or defect is well known as a capping in manufacturing of tablets (Prigge and Sommer, 2011). At 200 and 230 bar there were a problem in the feeding of Tylopur 604 and Glucidex16. The screw feeder struggle to rotate and push the powder towards rollers area. On the other hand, Avicel PH-101 produced ribbons with all pressure values which mean that the workability of Avicel PH101 is the best among the materials used. This is due to the high plasticity of Avicel PH-101 which makes it produce ribbons even at a low pressure of 30 bar.

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Force (μN)

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7

200 180 160 140 120 100 80 60 40 20 0 0

20

40

60

80

100

120

100

120

100

120

Force (μN)

Displacment (nm) 200 180 160 140 120 100 80 60 40 20 0 0

20

40

60

80

Force (μN)

Displacment (nm) 200 180 160 140 120 100 80 60 40 20 0 0

20

40

60

80

Displacment (nm) Fig. 7. The plastic region of force displacement curve that fits Eq. (5). ( pharmatose 200 M, Avicel PH-101).

CaCO3,

Fig. 6. The linearized form of the Hertz equation to find the elastic penetration limit. ( CaCO3, pharmatose 200 M, Avicel PH-101).

6.4. Width of ribbon The width of the rollers used in this study was 4 cm. The ribbons produced at 100 bar by different materials had different widths. Avicel PH-101, Tylopur 604 and Glucidex1 6 had the higher average width of 4 cm which is the width of the roller, followed by Pharmatose 200 M with an average width of 3.3 cm, followed by sodium carbonate with 3.2 cm and then calcium carbonate with 2.9 cm. This may be due to the pressure along the rollers, which is highest in the centre and lower at the sides (Cunningham et al., 2010). For powder with low hardness, the plastic deformation of the material is high so the pressures experienced on the rollers sides were sufficient enough to squeeze and bond particles together. This was not the case for materials with lower plastic deformability, such as Pharmatose 200 M, sodium carbonate and calcium carbonate, where the pressure was insufficient to bond the material to produce full width ribbons. 6.5. Hydraulic pressure versus ribbon strength and porosity Fig. 8 and Fig. 9 show the effect of hydraulic pressure on strength and porosity of the ribbon. As shown in Fig. 8, for all

Table 5 The yield strength of three materials used in this study. Material

Yield strength (GPa)

Calcium carbonate Pharmatose 200M Avicel PH-101

0.62 0.168 0.007

materials, increasing the pressure caused an increase in the ribbon tensile strength which is in agreement with previous studies (Inghelbrecht and Paul Remon, 1998; Osborne et al., 2013; Rambali et al., 2001; Kleinebudde, 2004) which showed that the applied pressure of the rollers compactor has the largest effect on the strength and porosity of the ribbon. In all cases, increasing hydraulic pressure caused an increase in ribbon strength and decrease in ribbon porosity. Upon comparing this increase in the strength of the ribbons of different materials, the Avicel PH101 showed the greatest increase in strength value from 1 to approximately 16 MPa, upon increasing the pressure from 30 to 230 bar respectively. The opposite was seen for calcium carbonate with smaller increase in the strength of the ribbon even at high pressure. Other materials are in the middle according to their hardness.

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20

Ribbon strength (MPa)

Ribbon strength (MPa)

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15 10 5 0 0

50

100

150

200

2.5 2 1.5 1 0.5 0

250

50

0

15 10 5 0 0

50

100

150

200

0.2 0 100

Ribbon strength (Mpa)

Ribbon strength (MPa)

200

300

Hydraulic pressure (bar)

4 2 0 150

250

0.4

0

6

100

200

0.6

250

8

50

150

0.8

Hydraulic pressure (bar)

0

100

Hydraulic pressure (bar)

Ribbon stength (MPa)

Ribbon Strength (MPa)

Hydraulic pressure (bar)

200

0.6 0.45 0.3 0.15 0 0

250

Hydraulic pressure (bar)

50

100

150

200

250

Hydraulic pressure (bar)

Ribbon strength (MPa)

20 15 10 5 0 0

50

100

150

200

250

Hydraulic pressure (bar) Fig. 8. Effect of hydraulic pressure on ribbon tensile strength.

Avicel PH 101,

Glucidex16, +Tylpor 604,

The deformability of Avicel PH-101 caused greater difference between the ribbon strengths for Avicel PH-101 in comparison to the other materials, as the pressure increased. In contrast to the strength, porosity decreased for all materials upon increasing the hydraulic pressure as shown in Fig. 9. The decrease was most significant for Avicel PH-101 and the less decrease was for calcium carbonate. Figs. 8 and 9 strongly suggest that the applied pressure between the two rollers is an important parameter. The workable pressure range of the equipment, which produces ribbons with suitable mechanical properties, become larger with increasing plastic deformation of material, this is because even at low pressure there

pharmatose 200 M, ~sodium carbonate,

calcium carbonate

is enough force to bond the particles and at high pressure the plastic deformation is still dominant. 6.6. Single particle hardness and ribbon strength Fig. 10 shows the tensile strength of the ribbons produced by powders of different materials, represented by their hardness, produced by different hydraulic pressures. It can be seen that with all hydraulic pressures, ribbons produced from low hardness powder almost has higher strength and the opposite for ribbons produced with high hardness powder which produced weak ribbons.

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0.7

Average Ribbon porosity

0.6 0.5

Calcium carbonate

0.4

Sodium carbonate Pharmatose 200M

0.3

Glucidex 6 0.2

Tylpor 604 Avicel PH-101

0.1 0 0

50

100

150

200

250

Hydraulic pressure (bar)

Fig. 9. Effect of hydraulic pressure on ribbon porosity.

It can be also seen that the difference in tensile strength between Avicel PH-101 and other materials increased with increasing of the pressure and reached maximum value at hydraulic pressure of 230 bar. Fig. 11 shows SEM images of the ribbon surface produced from different materials at a hydraulic pressure of 100 bar taken by Camscan S2, UK. Comparing Fig. 11 with Fig. 4, It can be shown that the number of particles that keep their shape as a single particle and not deform is higher in the powder of high hardness in comparison to the powder of low hardness. For example Avicel PH101 primary particles are needle shape whereas it is difficult to identify any needle shape particle in the ribbon. The same case can be observed for Glucidex16 and Tylopur 604. For Pharmatose 200 M, The primary particle is tomahauk like shape and some nondeformed particles in the ribbon can be identified. That suggests that the amount of deformation of particles in the ribbon is inversely related to the hardness of a single particle. This could also explain why the strength and porosity of the ribbon is related to the hardness of the single particle. With a material of low hardness, such as Avicel PH-101, the particles are deformed and create a solid

15

30 bar Ribbon stremgth (MPa)

Ribbon stremgth (MPa)

1.5

1

0.5

0

150 bar

10

5

0 0.4

1.4

2.4

0.4

20

70 bar Ribbon stremgth (MPa)

Ribbon stremgth (MPa)

6 5 4 3 2 1

1.4

2.4

Nano-indentation hardness (GPa)

Nano-indentation hardness (GPa)

0

200 bar

15 10 5 0

0.4

1.4

2.4

0.4

Nano-indentation hardness (GPa)

10

20

100 bar

8 6 4 2 0

1.4

2.4

Nano-indentation hardness (GPa)

Ribbon strength (MPa)

Ribbon stremgth (MPa)

9

230 bar

15 10 5 0

0.4

1.4

2.4

Nano-indentation hardness (GPa)

0.4

1.4

2.4

Nano-indentation hardness (GPa)

Fig. 10. The relation between nano-indentation hardness and ribbon tensile strength produced at different hydraulic pressures ( pharmatose 200 M, D sodium carbonate, calcium carbonate).

Avicel PH 101,

Glucidex16, +Tylpor 604,

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Fig. 11. SEM images for the surface of the ribbon produced using three different materials at 100 bar.

bridge between each other which makes the ribbon harder and less porous. With using a material of higher hardness, the particles are less deformed so the area of contact between them was less which caused the ribbons to have less strength and higher porosity. The images in Fig. 11 shows that the plastic flow between the particles of a material with a low hardness is higher compared to a material with a higher hardness value and therefore requires less pressure.

shown in Fig. 12. It can be seen that as hardness increases the average porosity increases too. As with the ribbon strength the porosity of the ribbon produced from low hardness powder such as Avicel PH-101 decreased largely with an increase of hydraulic pressure, whereas the decrease is less as the hardness of the powder increase.

6.7. Single particle hardness and ribbon porosity

Table 6 shows the maximum applied stress on material for different hydraulic pressures determined by Johanson’s theory and as calculated by Eq. (11) and as described in Section 4. By comparing the values of the yield strength of the material listed in

Porosity of ribbons produced by different materials at different hydraulic pressure was linked to the single particle hardness as

6.8. Maximum normal stress applied between the two rollers

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30 bar

150 bar

0.5

0.64

Average porosity

Average porosity

0.8

0.48 0.32 0.16

0.4 0.3 0.2 0.1 0

0 0.4

0.9

1.4

1.9

2.4

0.4

2.9

Nano-indentation hardness (GPa)

1.4

1.9

2.4

2.9

200 bar

0.5 Average porosity

Average porosity

0.9

Nano-indentation hardness (GPa)

70 bar

0.5 0.4 0.3 0.2 0.1

0.4 0.3 0.2 0.1 0

0 0.4

0.9

1.4

1.9

2.4

0.4

2.9

100 bar

0.5

0.9

1.4

1.9

2.4

2.9

Nano-indentation hardness (GPa)

Nano-indentation hardness (GPa)

230 bar

0.4

0.4

Average porosity

Average porosity

11

0.3 0.2 0.1

0.32 0.24 0.16 0.08

0

0 0.4

0.9

1.4

1.9

2.4

2.9

0.4

0.9

1.4

1.9

2.4

2.9

Nano-indntation hardness (GPa)

Nano-indentation hardness (GPa)

Fig. 12. The relation between nano-indentation hardness of the material and the average ribbon porosity produced at different hydraulic pressure ( Glucidex1 6, +Tylpor604, pharmatose 200 M, calcium carbonate, 4 sodium carbonate).

Table 5 with maximum applied stress listed in Table 6, it can be seen that the applied stress on Avicel PH-101 during the roller compaction is higher than the yield strength of the material at hydraulic pressure of 20 bar and above. This explains why the ribbons of Avicel PH-101 are strong at almost all the applied pressure. The particles were plastically deformed which create strong bonds between them. The case is almost the opposite for

Avicel PH 101,

calcium carbonate, the maximum stress applied for hydraulic pressures above 215 bar are less than the yield strength of the material. For Pharmatose 200 M the particles start to yield around 60 bar which explain the big jump in the tensile strength of the ribbons produced at 30 bar and 70 bar in Fig. 8. Fig. 13 shows SEM images of ribbon for different materials produced under different hydraulic pressures which covering stresses lower and higher than

Table 6 Maximum applied stress on the powder calculated by Eq. (11) for different hydraulic pressures. Hydraulic pressure (bar)

Roll force (KN)

20 30 40 60 70 80 100 120 140 150 160 180 200 215 230

8.29 12.44 16.59 24.88 29.03 33.17 41.47 49.76 58.05 62.2 66.35 74.64 82.94 89.16 95.38

Maximum normal stress at angle zero between the roller (GPa) Avicel PH-101

Ph.200M

Calcium carbonate

0.021 0.0315 0.042 0.063 0.073 0.084 0.105 0.126 0.147 0.157 0.168 0.189 0.210 0.226 0.241

0.05 0.075 0.100 0.150 0.176 0.201 0.251 0.301 0.351 0.376 0.401 0.451 0.501 0.539 0.577

0.052 0.078 0.104 0.155 0.181 0.207 0.259 0.311 0.362 0.388 0.414 0.466 0.518 0.557 0.595

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Fig. 13. SEM for ribbon surfaces (top: calcium carbonate, left 100 bar and right 230 bar,Middle Ph.200 M, left 30 bar and right 70 bar, bottom: Avicel PH-101; right 30 bar and 70 bar).

the yield stress of the material. For calcium carbonate and Pharmatose 200 M ribbons produced by 230 bar and 70 bar respectively, we can see some flat surfaces and this is believed to be due to the exceeding the yield stress of the powder and as shown in Table 6. For Avicel PH-101 and even with ribbon produced using low hydraulic pressure, the shape of the particles has changed because the applied stress on the powder was higher than the yield strength. 7. Conclusion This study showed that the hardness of the primary particles play an important role in controlling the final ribbon properties produced during the roller compaction. For the studied materials, It was found that the ribbon properties were related to the nano-indentation hardness of the primary single particle; the higher the hardness of the material the lower the strength and also, the higher the porosity of the produced ribbon for all investigated hydraulic pressures. It was

also found that the low hardness materials produced wider ribbons since the pressure on the roller sides was enough to bond the powder particles together. Comparing the value of the yield strength of the material with the maximum applied stress on the particles showed a good method to predict the workability of the powder for roller compaction process. If the maximum applied stress on the powder in roller compactor is higher than the yield strength of the powder, the particles will plastically deformed or fractured and create strong bond between each other and consequently produce strong ribbon. If it is less the particles will interlock with each other and hence produce weak ribbon. References Askeland, D.R., 1998. The Science and Engineering of Materials. Stanely Thomas Ltd., Cheltenham, UK. Bacher, C., Olsen, P.M., Bertelsen, P., Kristensen, J., Sonnergaard, J.M., 2007. Improving the compaction properties of roller compacted calcium carbonate. Int. J. Pharm. 342, 115–123.

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Roller compactor: The effect of mechanical properties of primary particles.

In this study, the nano-indentation hardness of a single primary particle was measured for six different materials; microcrystalline cellulose, hydrox...
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