Compression and mechanical properties of directly compressible pregelatinized sago starches

Powder Technology 269 (2015) 15–21

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Compression and mechanical properties of directly compressible pregelatinized sago starches Riyanto Teguh Widodo a,⁎, Aziz Hassan b a b

Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

a r t i c l e

i n f o

Article history: Received 24 January 2014 Received in revised form 14 May 2014 Accepted 15 August 2014 Available online 24 August 2014 Keywords: Sago Starch Pregelatinized Compressibility Compactibility

a b s t r a c t This study investigates the compression and mechanical properties of directly compressible pregelatinized sago starches in comparison with Spress® B820 and Avicel® PH 101. The sago starch is pregelatinized at 65 °C with different pregelatinization times of 15, 30, 45, and 60 min, creating samples PS1, PS2, PS3, and PS4, respectively. Compressibility of the powders is analyzed by Heckel and Kawakita equations. The compressibility of sago starch is found to be lower than that of its pregelatinized forms, and the compressibility increases with an increase in the pregelatinization time. Avicel® PH 101 is the most compressible among the powders evaluated, followed by PS4, Spress® B820, PS3, PS2, PS1, and sago starch. As for mechanical properties, Avicel® PH 101 is found to have the highest radial tensile strength and the hardest compacts, indicating that it has the highest compactibility, followed by Spress® B820, PS4, PS3, PS2, PS1, and sago starch. © 2014 Elsevier B.V. All rights reserved.

1. Introduction Starch is widely used as a pharmaceutical excipient, primarily in tablet formulations, functioning as a diluent, binder, and disintegrant [1,2]. Worldwide, corn starch is the most widely used starch in tablet formulations owing to its availability [3]. Because of compression problems, native starches are not suitable for use as excipients in direct compression formulations [4,5]. Pregelatinization is a proven method that renders starches directly compressible [6,7]. As an example, corn starch has been successfully pregelatinized and is commonly used as a directly compressible excipient with the commercial name Spress® B820 [8]. Direct compression is a technique involving compaction of a bulk material whose ingredients are composited to form tablets [9]. Mixing and compressing are the only steps involved in direct compression for the production of tablets, making it preferable in tablet production. Malaysia is one of the leading sago starch-producing countries in the world [10], mainly for use in food products [11]. Literature reviews show no report as yet on the application of a local sago starch for a directly compressible material in tableting. This study investigates the compression and mechanical properties of pregelatinized sago starch as a directly compressible excipient, and compares it with Spress® B820, a similar existing product; and Avicel® PH 101, a

⁎ Corresponding author. Tel.: +60 3 79675786. E-mail address: [email protected] (R.T. Widodo).

http://dx.doi.org/10.1016/j.powtec.2014.08.039 0032-5910/© 2014 Elsevier B.V. All rights reserved.

purified-partially depolymerized cellulose with extremely good binding properties in direct compression. 2. Experimental 2.1. Materials This study used a local sago starch (food grade; Nee Seng Ngeng & Sons, Sago Industries Sdn Bhd) and pregelatinized sago starches. In addition, we used a commercially available pregelatinized corn starch called Spress® B820 (lot S0615476; GPC, Muscatine, IA, USA), as well as the product Avicel® PH 101 (lot 11363; Fluka, Cork, Ireland). 2.2. Preparation of pregelatinized sago starches Pregelatinized sago starches (PS) were prepared according to Odeku et al. [12] and Adedokun and Itiola [13] with modifications. An aqueous slurry of 20% (w/v) sago starch was heated in a water bath (Grant SUB 36, Royston, England) at 65 °C with stirring at 700 rpm (WiseStir™ HD-30D; Daihan Scientific Co., Seoul, Korea) for 15 min (sample labeled PS1). The resulting paste of sago starch was dried in an oven (WTB Binder, Geprcifte Sicherheit, Germany) at 40 °C for 48 h. The dried mass was then powdered in a laboratory cutter mill (MX-895M, Selangor, Malaysia) to produce course powders. All of the starches were passed through a sieve (180-μm aperture) and stored in a tightly sealed white container before use. Three more batches were prepared with different heating times of 30 (PS2), 45 (PS3), and 60 min (PS4).

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2.3. Scanning electron microscopy

calculate relative density (D), porosity (ε), and degree of volume reduction (C) of the compact at pressure P using the formulae

Powder samples were mounted on a stub and coated with gold. Three-dimensional images of the powder samples were taken with a scanning electron microscope (FEI Quanta 200 FESEM, Eindhoven, Holland) with the accelerating voltage ranging from 10 to 12.5 kV.

D ¼ ρA =ρT ;

ð2Þ

ε ¼ 1−D;

ð3Þ

C ¼ 1−ρ0 =ρA ;

ð4Þ

2.4. Particle size determination Particle size was determined with a light microscope (Nikon Eclipse 80i; Nikon Instruments Inc., Kanagawa, Japan). Diameter of 300 particles projected on the computer screen was measured and the mean projected diameter was calculated automatically by NIS Element D2.30 computer software.

where ρA is the apparent density of the compact at pressure P. 2.9. Analysis of compression properties

2.5. Moisture content

Compression properties of the powder compacts were analyzed according to the Heckel and the Kawakita equations [8],

A sample of the powder (1 g) was dried in an oven at a temperature of 100–105 °C for 4 h. The percentage loss in weight was calculated as the moisture content.

ln

2.6. Densities

1 ½1−D

 ¼ kP þ A;

P=C ¼ P=a þ 1=ab;

The bulk density (ρ0) and tapped density (ρt) of the powders were determined using a tapped density tester (JV2000; Dr. Schleuninger Pharmaton AG, Solothurn, Germany). A 250-mL glass cylinder was filled with 100 g of powder sample and placed on top of the tapped density tester and the bulk volume was recorded. The cylinder was then tapped 1000 times to a constant volume and the tap volume was recorded. Bulk and tapped densities were calculated based on the ratio of weight to volume. The procedure was done in triplicate. The mean and standard deviations were measured in a process modified from previous studies [14,15]. The true density (ρT) of the materials was determined by a helium pycnometer (AccuPyc 1330; Micromeritics, Norcross, USA), wherein the powder sample was weighed and loaded into the sample cell, and the true volume was obtained by calculating the difference in helium pressure before and after loading the sample. Each sample was tested in triplicate [16]. 2.7. Total powder porosity The total porosity (ε) of a powder was calculated from the equation [17,18]   ρ 1− 0  100%; ρT



ð5Þ

ð6Þ

where k, A, a, and b are all constants. Heckel plots of ln(1 / [1 − D]) versus P were established. The slope of the linear plot indicated the value of the constant k, whereas the intercept of the plot gave the value of the constant A. The constant k reflects the deformation of the particle under compression, and the reciprocal of constant k is known as the mean yield pressure (Py) of the powder. The constant A is related to the particle rearrangement and die filling before deformation and the bonding of the discrete particles, and was used to calculate the relative density (Da) using the formula −A

Da ¼ 1–e

:

ð7Þ

The relative density at zero compression pressure, D0, is related to the initial rearrangement phase as a result of die filling; while the relative density, Db, describes the rearrangement phase at low pressure, and can be calculated from the formula Db ¼ Da –D0 :

ð8Þ

where ρT is the true density and ρ0 is the bulk density of the powder. The value for ε was calculated three times using the triplicate values obtained for ρT and ρ0, and an average for ε was then obtained from these three calculated values.

The Kawakita equation (Eq. (6)) was used to study the relationship between volume reduction of a powder and the pressure applied. The constants a and b can be determined by constructing a plot of P/C versus P. In this plot, the constant a is indicative of the total volume reduction of the powder bed, while the constant b is indicative of the plasticity of the powder, and its reciprocal value (Pk) is related to the yield strength of the particles.

2.8. Preparation of compacts

2.10. Analysis of mechanical properties

An Enerpac GA3 single punch machine (Globe Pharma, New Brunswick, NJ) equipped with a set of round flat-faced stainless steel toolings with a diameter of 8.00 mm was used in the preparation of compacts. Prior to the compression, a suspension of magnesium stearate in alcohol 95% was used to lubricate the punch faces and the die wall. Ten different compression pressures (from 20 to 200 MPa) were used to prepare the compacts from each material. The powder sample (300 ± 3 mg) was loaded manually into the die and the determined compression pressure was applied for 3 s [1]. The compact weight, hardness, and the dimensions of diameter and thickness were measured after being in storage for 24 h [19]. These data were used to

The mechanical properties of the powder compacts were evaluated by calculating the tensile strength, T using the formula

εðtotalÞ ¼

ð1Þ

T ¼ 2 F=πdt;

ð9Þ

where F is the force required to fracture the compact determined by a tablet hardness tester (Model 6D, Dr. Schleuniger Pharmatron, New Hampshire, USA), d is the diameter of the compact, and t is thickness of the compact. The use of tensile strength in the evaluations was to allow the compact dimensions to be taken into consideration. All measurements were taken in triplicate.

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2.11. Data analysis The difference in the mean values of the data was analyzed by using a t-test and by analysis of variance (ANOVA) tests. Results with p b 0.05 were considered to be significantly different. 3. Results and discussion 3.1. Scanning electron microscopy Fig. 1 shows the SEM images of Avicel® PH 101, Spress® B820, sago starch, and the four samples of pregelatinized sago starch. Sago starch granules are found to have oval-to-round shapes with a smooth surface texture (Fig. 1c). These observations are similar to previous studies [20, 21]. After pregelatinization for 15 min (PS1) and 30 min (PS2), the

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starch granules show the initial stages of swelling, though a small portion of the particles is gelatinized with no observable effect on the surface texture and granule shape (Fig. 1d and e, respectively). By prolonging the heating time to 45 min (PS3) and 60 min (PS4), more sago starch granules are gelatinized, resulting in the loss of surface smoothness and the appearance of more irregular shapes (Fig. 1f and g, respectively). This more marked change at longer heating times is because of the higher amount of water that diffuses into the starch granules and the amount of heat received by the starch granules during the prolonged heating time. As a result, the starch granules swell to a greater extent and the crystallites melt, causing more granules to be gelatinized and leading to the greater change in the shape and size of the starch granules [22,23]. In general, Fig. 1 shows that Avicel® PH 101 has the highest degree of irregular shapes and surface roughness, followed by Spress® B820, PS4, PS3, PS2, PS1, and sago starch.

Fig. 1. SEM images of (a) Avicel® PH 101, (b) Spress® B820, (c) sago starch, (d) PS1, (e) PS2, (f) PS3, and (g) PS4.

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Table 1 Mean particle size, moisture content, densities, and porosity of each powder sample. Powder

Avicel PH 101 Spress® B820 Sago starch PS 1 PS 2 PS 3 PS 4 a b c d

Mean particle size, diameter (μm) ± SDa

% moisture content ± SDb

Density (g/cm3) ± SDc True (ρT)

Bulk (ρ0)

Tap (ρt)

56.70 89.30 32.10 75.9 86.70 87.80 88.00

5.19 9.91 12.81 11.86 11.72 11.38 10.39

1.58 1.50 1.55 1.52 1.52 1.52 1.51

0.35 0.64 0.63 0.53 0.53 0.53 0.52

0.44 0.71 0.73 0.63 0.63 0.62 0.61

± ± ± ± ± ± ±

11.51 20.29 10.72 20.97 19.78 16.52 18.98

± ± ± ± ± ± ±

0.06 0.02 0.12 0.06 0.08 0.13 0.41

± ± ± ± ± ± ±

0.00 0.00 0.00 0.00 0.00 0.00 0.00

± ± ± ± ± ± ±

0.00 0.00 0.00 0.01 0.00 0.00 0.01

± ± ± ± ± ± ±

% porosity (ε) ± SDd

0.00 0.00 0.00 0.01 0.01 0.01 0.01

77.84 57.33 59.35 64.91 65.13 65.13 65.34

± ± ± ± ± ± ±

0.00 0.00 0.00 0.38 0.00 0.00 0.38

n = 300 for each powder. n = 3 for each powder. n = 3 for each powder at every density. n = 3 for each powder.

3.2. Particle size, moisture content, densities, and porosity The mean particle size, moisture content, densities, and powder porosity for the entire sample powders are presented in Table 1. The mean diameter for sago starch is found to be in agreement with that reported by Ahmad et al. [20] and Wang et al. [24]. Spress® B820 shows the largest mean diameter, followed by PS4, PS3, PS2, PS1, Avicel® PH 101, and sago starch. All of the examined powders meet the United States Pharmacopeia requirements for moisture content specifications. The true density of Avicel® PH 101 is the highest, followed by sago starch, PS1 = PS2 = PS3, PS4, and Spress® B820. As for bulk density, Spress® B820 exhibits the highest value, followed by sago starch, PS1 = PS2 = PS3, PS4, and Avicel® PH 101. The tapped density of sago starch is the highest, followed by that of Spress® B820, PS1 = PS2, PS3, PS4, and Avicel® PH 101. Avicel® PH 101 shows the highest powder porosity, followed by PS4, PS3 = PS2, PS1, sago starch, and Spress® B820. These results show that the process of pregelatinization causes a significant increase (p b 0.05) in both the mean diameter and powder porosity of sago starch (p b 0.05) but decreases its densities significantly (p b 0.05). 3.3. Compression properties Fig. 2 shows the Heckel plots of the evaluated powders, and their related constants are listed in Table 2. The values for the constant k are obtained from the slope of the Heckel plots, with the linearity in the range of 0.9617–0.9984 for all of the powders evaluated. This strong linearity indicates that plastic deformation is dominant [25]. The mean yield pressure (Py), which is the reciprocal of k, can be understood as the pressure existing when the plastic deformation starts [26]. Thus, a lower value of Py indicates a greater plasticity of the materials [27]. The intercept of the plots give the value of the constant A, which is related to the particle rearrangement before deformation and bonding,

and reflects the densification of powders in the early stages of compaction. The constant D0 is the densification at zero pressure as a result of die filling, and is equal to the ratio of the bulk density at zero pressure and the true density (relative bulk density). The constant Db is the densification due to the movement and rearrangement of particles (densification of fragmentation), and the constant Da is the total densification of the plastic deformation before interparticle bonding becomes appreciable [28,29]. Referring to Table 2, the Py value for Avicel® PH 101 is lower than all of the starches, indicating that Avicel® PH 101 is the most plastic and that the onset of its plastic deformation occurs at the lowest pressures. In general, the Py value of sago starch is found to be higher than its pregelatinized forms (p b 0.05), which suggests that pregelatinized sago starches have greater plasticity than sago starch. The plasticity of PS4 was the highest among the pregelatinized sago starches, but was still slightly lower than that of Spress® B820 (p b 0.05). According to Bouvard [30], Nokhodchi et al. [31], and Patel et al. [32], materials with shapes that are more irregular, have rougher surfaces and a larger size will show lower Py values with higher compressibility. Our study finds that the sequence of decreasing powder Py values is in line with the increasing degree of irregularity in the particle shape (p b 0.05). However, Avicel® PH 101 is found to have the lowest Py value even though its average particle size is the second lowest among the powders evaluated. This indicates that the plastic deformation of Avicel® PH 101 is dominated by its irregular shape and rough surface texture (p b 0.05). In addition, structural analysis shows that Avicel® PH 101 is fibrous in nature, and such materials are known to exhibit excellent plastic deformation [33]. This study also finds that PS1 shows a lower plasticity than sago starch, although all of the factors discussed above are in favor for PS1 to have a higher plasticity. A possible explanation for this discrepancy is that the plastic deformation in sago starch and PS1 is dominated by the degree of irregularity in the particle shape (p b 0.05). This conclusion is based on the fact that the average particle sizes of the sago starch and PS1 are significantly different (p b 0.05), while SEM analysis shows no obvious dissimilarity in the shapes and surface textures of sago starch and PS1 (Fig. 1c and d, respectively).

Table 2 Heckel plot constants and parameters for the powders in this study. Powder

Fig. 2. Heckel plots of the ln[(1 − D)−1] values of the powders versus compression pressure, P.

Avicel PH 101 Spress® B820 Sago starch PS1 PS2 PS3 PS4

Plot constants

Parameters

k

A

R2

D0

Da

Db

Py

0.0106 0.0104 0.0018 0.0017 0.0029 0.0035 0.0080

0.8147 0.9973 0.9606 0.9036 0.8880 0.8094 0.7700

0.9709 0.9754 0.9984 0.9939 0.9852 0.9617 0.9680

0.22 0.43 0.41 0.35 0.35 0.35 0.34

0.56 0.63 0.62 0.59 0.59 0.55 0.54

0.34 0.20 0.21 0.24 0.24 0.20 0.20

94.34 96.15 555.56 588.24 344.83 285.71 125.00

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The D0 value for Avicel® PH 101 is the lowest among the powders tested (Table 2). This initial densification value is likely a result of the die filling being affected by the fibrous rod-like structure of Avicel® PH 101 [34]. D0 value because sago starch exhibits a smaller particle size than its pregelatinized forms. However, Spress® B820 shows a higher D0 value than sago starch although it has a larger average particle size. This is likely due to Spress® B820 possessing a larger range of particle sizes, whereby its smaller particles are able to fill the interparticle voids and form better densification [32]. Avicel® PH 101 shows the highest Db value, suggesting that Avicel® PH 101 experiences the most fragmentation among the powders tested at low pressure. Within the sago starch group, the Db values for PS1 and PS2 are higher than the sago starch. This is likely because of a fragility in the agglomerates of PS1 and PS2 resulting from the short pregelatinization process applied to these starches. The values of Db decrease when the pregelatinization time is increased, as is true for PS3 and PS4. This longer pregelatinization time presumably produces stronger agglomerates, thus resulting in lower fragmentation under low pressure. A lower value of Db is also an indication of the particles possessing a higher resistance to moving [34]. In comparison, the Db value for Spress® B820 is the same as those of PS3 and PS4. This study finds the ranking of Da values to be Spress® B820 N sago starch N PS1 N PS2 N Avicel® PH 101 N PS3 N PS4. The possession of a lower value of Da indicates that a powder has lower densification. It is observed that within the sago starch group, pregelatinization decreases the Da values (p b 0.05) and the Da values decrease with increasing particle size (p b 0.05). According to Ohwoavworhua et al. [34], the Da value will correlate with the particle contact area. This is confirmed in our powders, because the lowest Da value is exhibited by the powder with the largest particle size in the group (PS4) and, hence, the powder possessing the smallest contact area. Spress® B820 has the largest average particle size among the powders evaluated, but has the highest Da value. This is because the particle arrangement of Spress® B820 is able to form large surface contacts, as indicated by its highest initial densification value, D0 [35]. Avicel® PH 101 is found to have the lowest D0 value among the powders, but its Da value is between those of PS2 and PS3. This is because the particles of Avicel® PH 101 undergo the highest fragmentation (Db value), thereby resulting in particles with a higher surface area. Fig. 3 shows Kawakita plots for the powders evaluated in this study. The plots are linear with a correlation coefficient (R2) of 0.9953 and above. The Kawakita constants are tabulated in Table 3. The value of the constant a (i.e., slope) is indicative of a total volume reduction of the powder bed (compressibility), the value of Di(1 − a) is related to the initial relative density at low pressure, and b is a constant whose reciprocal value, Pk, is related to the yield strength of the particles [36]. Evaluating the values for the constant a, Avicel® PH 101 is the most compressible among the powders evaluated. Within the sago starch category, PS4 is the most compressible, followed by PS3, PS2, PS1, and sago starch. This indicates that pregelatinization significantly increases

the compressibility of the sago starch (p b 0.05), and that the degree of compressibility increases as the pregelatinization time increases (p b 0.05, R2: 0.9953–0.9999). As for Spress® B820, its compressibility is significantly higher (p b 0.05) than that of PS3 but significantly lower (p b 0.05) than that of PS4. In Table 3 we can see that the Di(1 − a) value for sago starch is the highest, followed by that of PS1, PS2, PS3 Spress® B820, PS4, and Avicel® PH 101. This indicates that sago starch has the highest packing at low compression pressures. These results are in good agreement with the understanding that the packing of a powder under a compression pressure is determined by its deformation tendency [37], and this study shows that the Di(1 − a) values correspond to their plasticity (Py value). Evaluating the values for the constant b, Avicel® PH 101 exhibits the lowest Pk value among the powders evaluated. It can also be observed that the Pk values of the pregelatinized sago starches are higher than that of the sago starch (p b 0.05) with the exception of PS1, whose Pk value is significantly lower than that of the sago starch (p b 0.05). Generally, the Pk values of the sago starch increases as the pregelatinization time increases (p b 0.05), although PS3 demonstrates a higher Pk value than PS4 (p b 0.05). As for Spress® B820, its Pk value is significantly higher than that of PS4 (p b 0.05) but lower than that of PS3 (p b 0.05). According to Alebiowu and Itiola [36], the Pk value relates to the amount of plastic deformation occurring during the compression process, which is responsible for the tensile strength value, and where a lower value of Pk means a higher tensile strength. The Pk values are inconsistent with the tensile strength findings in this study (Fig. 4), except in the case of Avicel® PH 101, which is found to have the highest radial tensile strength at any value of applied compression pressure. The ranking of the tensile strengths from largest to smallest is then followed by Spress® B820, PS4, PS3, PS2, PS1, and sago starch. This inconsistency of the tensile strength values and the Pk values may be because of the different capacities of the powders to form compacts under the predetermined range of compression pressures used in this study (20–200 MPa). For this reason, plots of the Kawakita equations in Fig. 3 use different ranges of compression pressures. Sago starch powder only forms compacts under a short range of compression pressures (40–140 MPa), PS1 and PS2 form compacts under an increased range

Fig. 3. The graphs of the P/C values of the powders versus compression pressure, P.

Fig. 4. Plot of the tensile strength of each powder versus compression pressure.

Table 3 Kawakita plot constants for the powders in this study. Powder

a

b

R2

Di(1 − a)

Pk

Avicel PH 101 Spress® B820 Sago starch PS1 PS2 PS3 PS4

0.7868 0.6174 0.4534 0.5216 0.5860 0.5970 0.6609

0.1621 0.0646 0.0887 0.0889 0.0633 0.0515 0.0658

0.9999 0.9994 0.9989 0.9993 0.9990 0.9953 0.9957

0.21 0.38 0.55 0.48 0.41 0.40 0.34

6.17 15.48 11.27 11.25 15.80 19.42 15.20

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of compression pressures (40–200 MPa), while PS4 forms compacts at a larger range of compression pressures (20–200 MPa). The Kawakita parameter is pressure dependent, so such a large variation of compression pressure ranges will impact the curve fitting when P/C is plotted against P. The poor correlation between the yield strengths (Pk) obtained from the Kawakita equation and the tensile strengths is in agreement with the review reported by Denny [38], who stated that there have not been good correlations between the yield strength (Pk) and the mechanical properties of a powder. 3.4. Mechanical properties The compact hardness and radial tensile strength indicates the mechanical properties of the directly compressible materials. As shown by Figs. 4 and 5, strong linear relationships are found for the plots of tensile strength versus compression pressure (R2: 0.8884–0.9961) and the plots of hardness versus compression pressure (R2: 0.9168–0.9914). At any compression pressure value, Avicel® PH 101 shows the highest radial tensile strength and the hardest compacts of all of the powders, followed by Spress® B820, PS4, PS3, PS2, PS1, and sago starch (Figs. 4 and 5). This indicates that Avicel® PH 101 has the highest compactibility and undergoes the greatest plastic deformation, as is confirmed by it possessing the lowest Py value. This ranking of the compactibility of our samples is also supported by the respective area under the curve (AUC) of the tensile strength versus pressure [39], where a larger AUC indicates a higher compactibility (Fig. 4). The AUC follows the same ranking in our samples as the compactibility, with the AUCs of Avicel® PH 101, Spress® B820, PS4, PS3, PS2, PS1, and sago starch calculated as 1270.6, 446.8, 392.7, 222.7, 200.1, 134.8, and 54.8, respectively. The excellent hardness of Avicel® PH 101 compacts has a contribution from hydrogen bonding. The bonding formation is facilitated by the plastic deformation and the presence of an optimum moisture content (5.19%) within the porous structure of Avicel® PH 101, where the moisture acts as an internal lubricant to facilitate the flow within the individual microcrystalline particles during plastic deformation, thus enforcing the formation of hydrogen bonding [5]. In comparison, the hardnesses and tensile strengths of Spress® B820, PS, and sago starch are much lower than that of Avicel® PH 101 at any of the applied compression pressure values. This is because the plastic deformation of starches that occurs during compression develops too slowly to form interparticle bonding, as indicated by the Py values of these samples. Within the sago starch category, pregelatinization greatly improves (p b 0.05) the compactibility, and therefore the hardness and tensile strength, of these samples. Sago starch, PS1, PS2, and PS3 are not able to form compacts at 20 MPa, indicating that they require more compression pressure to initiate the plastic deformation. The compacts of these samples can only be formed at compression pressures of 40 MPa and above, with the hardness and tensile strength of the compacts differing

Fig. 5. Plot of the hardness of each powder versus compression pressure.

significantly (p b 0.05) (Figs. 4 and 5). Under the conditions of these tests, the hardness of the sago starch compacts is less than 60 N, indicating that these compacts are generally weak [12], and that the compacts exhibit brittle fracturing at compression pressures above 140 MPa. Meanwhile, PS4 is able to form compacts at 20 MPa, similar to Avicel® PH 101 and Spress® B820, but the tensile strength of PS4 compacts is lower than that of Spress® B820 (p b 0.05) at any of the compression pressures. This study observes that the order of increasing compact hardness and tensile strength among sago starch, PS and Spress® B820 is influenced by the increasing particle size and particle shape irregularity, and by the decreasing moisture content (p b 0.05). As shown in the case of sago starch, a larger number of smaller particles with larger contact points is produced during compression, causing the distribution of pressure applied on each contact point to be relatively lower and therefore producing softer compacts [8]. According to Kibbe [1], starches poorly compact; therefore, starches with too low of a moisture content are not suitable as direct compression materials. Hence, a moisture content at an optimum state is needed to enhance compressibility and to facilitate plastic deformation of glassy starches [40]. An optimum quantity of adsorbed water will increase the number of solid bridges and enhance particle–particle interactions. The moisture may also penetrate between adjacent particles, resulting in stronger attraction forces. High moisture content, as shown by our sago starch sample, produces the weakest compacts. This is because of the formation of multilayer water or free water at the surface of the particles, thereby reducing the intermolecular attraction forces. 4. Conclusions This study confirms previous reports showing that pregelatinization is able to improve the compressibility and compactibility of a starch, and therefore showing the potential of pregelatinized sago starch (PS4) as a new directly compressible excipient in tablet formulations. We find that the compressibility of pregelatinized sago starch (PS4) is superior to Spress® B820 and inferior to Avicel® PH 101. However, the plasticity and the compactibility of pregelatinized sago starch is inferior to both Spress® B820 and Avicel® PH 101. Acknowledgments The authors acknowledge the financial support of the Ministry of Science and Technology Malaysia (IRPA Project No. 03-02-03 1006) and the University of Malaya (RG 159/11AFR). References [1] A.H. Kibbe, Handbook of Pharmaceutical Excipients, American Pharmaceutical Association and Pharmaceutical Press, London, 2000. 501–504 (522–527, 528–533). [2] R.F. Shangraw, Compressed tablet by direct compression, in: H.A. Lieberman, L. Lachman, J.B. Schwartz (Eds.), Pharmaceutical Dosage Forms: Tablets, Marcel Decker Inc., New York and Basel, 1989, pp. 195–247. [3] C.K. Riley, S.A. Adebayo, A.O. Wheatly, H.N. Asemota, Surface properties of Yam (Dioscorea sp.), starch powders and potential for use as binders and disintegrants in drug formulations, Powder Technol. 185 (2008) 280–285. [4] M. Jivraj, L.G. Martini, C.M. Thomson, An overview of the different excipients useful for the direct compression of tablets, Pharm. Sci. Technol. Today 3 (2) (2000) 58–63. [5] G.K. Bolhuis, Z.T. Chowhan, Materials for direct compaction, in: G. Alderborn, C. Nström (Eds.), Pharmaceutical Powder Compaction Technology, Marcel Dekker Inc., New York, 1996, pp. 419–500. [6] The British Pharmacopeia Commission, The British Pharmacopeia 2007, 2006. (London). [7] The United States of Pharmacopeial Convention, The United States of Pharmacopeia 30/The National Formulary 25: USP 30/NF 25, Port City Press, Baltimore, 2007. [8] Y. Zhang, Y. Law, S. Chakrabarti, Physical properties and compact analysis of commonly used direct compression binders, AAPS PharmSciTech 4 (4) (2003) 1–11. [9] J.K. Prescott, R.J. Hossfeld, Maintaining product uniformity and uninterrupted flow to direct compression tablet presses, Pharm. Technol. 18 (6) (1994) 99–114. [10] R.S. Singhal, J.F. Kennedy, S.M. Gopalakrishnan, A. Kaczmarek, C.J. Knill, P.F. Akmar, Industrial production, processing, and utilization of sago palm-derived products, Carbohydr. Polym. 72 (2008) 1–20.

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