Drug Development and Industrial Pharmacy, 23(7), 711-716 (1997)

RESEARCH PAPER

Evaluation of Era-Tab as a Direct

Compression Excipient
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Shu-Hui Hsu, Tong-Rong Tsai, Wen-Ho Chuo, and

Thau-Ming Cham*

School of Pharmacy, Kaohsiung Medical College, Kaohsiung, Taiwan,

Republic of China

ABSTRACT
For personal use only.

The physical and compressional properties of a modijied rice starch, Era-Tab, were
evaluated and compared with those of 4 commercially available direct compres-
sion excipients, namely, microcrystalline cellulose (Avicel PH-I Ol), partially
pregelatinized starch, spray-dried lactose (Super-Tab Lactose), and granular
dicalcium phosphate dihydrate (Emcompress). It was found that Era-Tab possessed
high flowability and adequate compressibility. The compacted material made with
Era-Tab has a higher crushing strength and a lower friability than 3 other direct
compression excipients, except microcrystalline cellulose. Tablets containing
terjenadine of the same degree of hardness ( 4 0 kg) were also prepared using
different direct compression excipients. The disintegration time of the tablets made
with Era-Tab was approximately 2.5 min. The maximum of the accumulated per-
centage of terjenadine releasedfrom the tablet reached 90%, and 63.2% of it was
released within 20 min. Both the powder characteristics and tablet properties show
that the modified rice starch, Era-Tab, is a useful product as a direct compres-
sion tablet excipient.

*To whom correspondence should be addressed.

71 1

Copyright 1997 by Marcel Dekker, Inc.

 712 Hsu et al.

INTRODUCTION disintegrant, respectively. The excipients were stored

under controlled temperature (25" * 1°C) and humid-
The direct compression method for the production of ity condition (RH = 45 * 1%) prior to study for at
tablets ofiers many advantages such as simplicity, reduc- least 2 weeks.
tion of labor costs, fewer manufacturing steps and pieces
of equipments, and increasing product stability (1-3). METHODS
Mainly, 4 types of direct compression excipients are
currently used in the pharmaceutical industry: (i) inor- Powder Characterization of Excipients
ganic compounds (e.g., dibasic calcium phosphate), (ii)
lactose (e.g., spray-dried lactose), (iii) microcrystalline Particle size distributions of excipients were deter-
cellulose, and (iv) partially pregelatinized starches. Each mined in triplicate by sieve analysis on an Alpine Air
of them has its own merits when used in direct compres- Jet Sieve (Alpine, Augsburg, Germany). The results
sion tablet formulation (4). were plotted on log-probability axes, and the geometric
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Due to its sensitivity to hydrophobic lubricants, such mean diameters (d,) were calculated. The flowability
as magnesium stearate, in the tablet formulation process, (angle of repose) of the excipients was measured accord-
partially pregelatinized starch did not gain popularity in ing to the fixed-funnel and free-standing-cone method.
the direct compression excipient market (4). Recently, The results of angle of repose are the mean of 5 mea-
it was reported that Proflo cornstarches and Preflo po- surements.
tato starches could be a potential for direct compression The true densities of the powders were determined by
of sustained-release tablets (5). gas pycnometry (Multi-Pycnometer, Quantachrome Co.,
Era-Tab is an agglomerated form of modified rice USA) using helium. By placing a powder carefully into
starch. It is primarily used in processed food and food a 100-ml measuring cylinder using a spatula until the
products. Era-Tab is intended to be used as a direct 100-ml volume mark was reached, the weight of the
For personal use only.

compression excipient and has been claimed to be com- powder could be determined. The bulk density (g/cm3)
patible with a wide range of pharmaceutical materials of each of the excipients was computed. Subsequently,
(6). Recently, the modified rice starch (also marketed as the cylinder was fixed onto the Vanderdamp Tap Den-
Primotab ET) had been reported to be suitable for di- sity Tester (VanKel Industries, Inc., USA), and the tap-
rect compression tablet formulations containing ox- ping procedure was performed. The volume readings
azepam (7). were taken at intervals of 500 taps. Then the tapped
The purpose of this investigation was to evaluate Era- bulk densities of the excipients were determined. The
Tab further as a direct compression excipient with re- results of the density determinations are the mean of 3
spect to its physical and tableting properties, and to determinations, with which the percentage porosity and
compare it with those of the 4 types of direct compres- percentage compressibility (8) were calculated.
sion excipients. The shape and surface characteristics of the powders
were examined in a scanning electron microscopy
(SEM) (S-2300, Hitachi, Japan). The specific surface
MATERIALS areas of the excipients were determined by the BET
method using the Micromeritics Flowsorb I1 2300
Microcrystalline cellulose N.F. (Avicel PH-101) (Micromeritics Co., Ltd., USA). Thermal analyses of
(Asahi Chemical Industry Co., Ltd., Japan), partially the powders were performed using a Perkin-Elmer dif-
pregelatinized starch (PPS) (Hui Ming Pharm. Co., ferential scanning calorimeter (DSC) (DSC7, Perkin-
Ltd., ROC), spray-dried lactose (Super-Tab Lactose) Elmer Co., USA), and the possible interactions between
(The Lactose Company of New Zealand Co., Ltd., New terfenadine and the respective excipient were estimated
Zealand), dicalcium phosphate dihydrate (Emcompress) from the DSC thermograms.
(Edward Mendell Co., Ltd., USA), and modified rice
starch (Era-Tab), (Erawan Pharmaceutical Research and Preparation and Characterization of Tablets
Laboratory Co., Ltd., Thailand) were used as supplied.
Terfenadine (Synsefarm, Co., Ltd.,8/0392010, Italy) Flat-faced placebo tablets each weighing 550 & 5 mg
was chosen as the model drug. Magnesium stearate were individually prepared by compressing the powder
(Wako Co., Ltd., Japan) and Primojel (AVEBE b.a., in a single-punch hydraulic press (Model-C, Freds.
The Netherlands) were used as lubricant and Carver Inc., USA). The tablet diameter was 1.25 mm
 Era-Tab as a Direct Compression Excipient 713

and the compression pressures used were 30, 50, 70, amounts of the dissolved drug were determined spectro-
100, 120, 150, 200, 250, and 300 kg/cm2, respectively. photometrically (UV-700, JASCO Co., Ltd., Japan) at
The tablets were weighed accurately and tested for 256 nm. For each sampling point, 6 tablets were tested
thickness, crushing strength (CT-5 engineering system for each formulation.
hardness tester, Nottm. Co., Ltd., England), and friabil-
ity (Erweka Instruments Inc., Germany) after storage
for 24 hr in a desiccator. The tensile strength of the RESULTS AND DISCUSSION
tablets was then determined (9). Powder Characteristics of 5 Direct Compression
Tablets containing terfenadine (Table 1) as the model Excipients
drug were prepared at predetermined compression pres-
sure for the same degree of hardness (=lo kg). After The physical characteristics of the 5 excipients are
ejection, the tablets were stored in a desiccator for 24 listed in Table 2 . The geometric mean diameter of Era-
hr prior to disintegration and dissolution testing. The Tab is 72 pm. It has an angle of repose of 34" and
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disintegration time of the tablets was determined with a percentage compressibility of 14%, both indicating good
disintegration apparatus (Ming-pen Machine Co., ROC) flowability (8). The SEM examination has shown that
adopting the method described in USP XXIII for un- Era-Tab particles are aggregates of a more spherical
coated tablets without the guide disk in place. The dis- shape with a main size range between 50 and 100 pm,
integration medium was distilled water maintained at similar to those reported by Bos et al. (7). It also ex-
37" k 0.5"C. The mean of 6 determinations was taken plains why Era-Tab has a good flowability, which co-
for each batch. incides with the results of geometric mean diameter. The
Dissolution tests were carried out with the USP geometric mean diameters and flowability of Avicel PH-
XXIII dissolution apparatus, (DT-610 JASCO CO., 101, Emcompress, and PPS are similar to those reported
Ltd., Japan) in 900 ml 0.1 N HCI maintained at 37" k previously (10,ll).
For personal use only.

0.5"C as dissolution medium, and the paddle speed was Differential scanning calorimetry (DSC) was used to
100 rpm. Samples of the drug solution passed through predict a possible incompatibility of terfenadine-excipi-
a 30-50 pm filter at 1, 2 , 3, 5, 7, 10, 15, 20, 30, 40, ent binary mixtures from the DSC profile. The results
60, 90, 120, and 180 min were collected, then the illustrate that the DSC thermogram of terfenadine shows

Table 1
Formulations, Disintegration Time, and Weibull Equation Parameters of Terfenadine Tablets
Formulation
Ingredient 1 2 3 4 5
Terfenadine 60mg 60mg 60mg 60mg 60mg
Era-Tab 450mg
Emcompress 450mg
Avicel PH-101 450mg
Super-Tab Lactose 450mg
PPS 45omg
Magnesium stearate 5mg 5mg 5mg 5mg 5mg
Premojel 35mg 35mg 35mg 35mg 35mg
Disintegration time (sec) 139.00 21.25 18.50 19.00 74.00
(* SD) (* 4.95) (* 1.92) (k 2.69) (* 1.22) (k 3.16)
Parametersa
Tiag
-0.2544 0.4512 -0.0728 0.7978 -0.2269
k 0.8162 0.5085 0.4996 0.4063 0.5050
Td 20.3055 7.3170 17.9411 15.6287 4.2957
M 90.0090 83.6665 78.7047 65.4983 81.8400
'Tag:the lag time; k: the shape parameter; Td: the time (min) when 63.2%of drug was released; M: the accumulated percentage re-
leased.
 714 Hsu et al.

Table 2
Physical Properties of 5 Excipients
Super-
Emcom Avicel Tab Starch
Excipients Era-Tab press PH-101 Lactose 1500
Geometric mean diameter dg (pm) 72 118 43 106 160
Geometric standard deviation a g 1.7 1.68 1.87 2.08 3.88
Correlation coefficient of particle size distribution 0.94 0.85 0.94 0.96 0.99
Angle of repose (deg) 33.69 36.53 53 75
I 49.27 41.94
True density (g/cm3) 1.47 2.29 1.51 1.66 1S O
Bulk density (g/cm3) 0.52 0.84 0.31 0.64 0.61
Ultimate tap density (g/cm3) 0.60 1.OO 0.46 0.83 0.87
0.29 0.71 1.04 0.25 0.98
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Specific surface area (m*/g)

the melting endothermic peak at 152.1"C (Fig. I), with terfenadine-Era-Tab mixture essentially reserves the
no apparent decomposition up to a temperature of parent peaks of the pure components. It implies that no
250°C. Era-Tab shows a broad endotherm ranging from interaction between terfenadine and Era-Tab was ob-
70" to 120°C. The DSC thermogram of the served. Thus, Era-Tab can be used in combination with

30
For personal use only.

22.5

7.5

Figure 1. DSC thermograms of Era-Tab, terfenadine, and Era-Tab + terfenadine mixture.

 Era-Tab as a Direct Compression Excipient 715

Table 3
The Physical Characteristics and Constants of the Excipients Derived from the Heckel Plots

Yield
Correlation Pressure
Slope Intercept Coefficient PY
Excipients (K) (4 (r) (kg/cm2) DL7 Da Dh
Era-Tab 0.017 0.75 0.98 58.8 0.35 0.53 0.12
Emcompress 0.005 1.13 0.99 200.0 0.37 0.68 0.31
Avicel PH-101 0.017 0.94 0.97 58.5 0.21 0.61 0.40
Super-Tab Lactose 0.006 1.13 0.98 178.6 0.39 0.53 0.14
PPS 0.013 0.87 0.96 75.2 0.41 0.58 0.17
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terfenadine in formulations. The DSC results also indi- Era-Tab

cate that there is no apparent interaction between Starch IS00
terfenadine and the other 4 excipients (The DSC ther- FE 4 O t 7 A
v
Emcompress
Avicel P H 101
mograms are not shown).

Tablet Characteristics of the 5 Excipients

Y

f Super-Tab Lactose

The relationship between applied pressure and the

For personal use only.

density of the powder columns was analyzed using the

Heckel plots (12-14). Using the initial linear portion of "
the Heckel plots, the physical characteristics and mate- 0 50 100 150 200 250 300 350
rial constants of the excipients were computed and are Pressure (kglcm')

shown in Table 3; while Do,D b , and D, are the densi-

fication at zero pressure, the densification due to particle Figure 2. Tensile strength as a function of compression pres-
movement and rearrangement, and the densification sure.
before interparticle bonding becomes appreciable, re-
spectively. rates of disintegration and dissolution. The disintegra-
In general, it is obvious that the variation in Do, D b , tion times of the terfenadine tablets are less than 3 min
and D,is primarily a function of particle shape. Avicel (Table l), indicating that tablets made with various ex-
PH-101, which is irregular in shape, gives a higher cipients exhibit good disintegration property. The ex-
value for Db; whereas Era-Tab, which is more spheri- perimental results on the release of terfenadine from the
cal, gives the lowest Db value. The yield pressure (p,)
values for Era-Tab and Avicel PH-101 were lower than
Era-Tab
those of Emcompress and Super-Tab Lactose, as shown Starch I500
in Table 3. From the results shown, Era-Tab was the A Emcompress
most ductile material, more plastic and easily compress- v Avicel PHlOl
Super-Tab Lactose
ible even at low compression pressures.
In Fig. 2, Avicel PH-101 and Era-Tab reveal the
highest tensile strength among the excipients under the
same compression pressure at pressures less than 200
kg/cm2. The friability of placebo tablets prepared from
these excipients decreases with increasing pressure (Fig.
= 0
50 50 100 150 200 250 300
3), and it can be seen that the friability of Era-Tab tab-
lets is relatively low over the range of pressure studied. Pressure (k g/cm *)
The bioavailability of an immediate-release orally
administered tablet is most likely to be controlled by its Figure 3. Friability as a function of compression pressure.
 716 Hsu et al.

tablets were interpreted using the Weibull equation (15), 2. E. J. Mendell, Manf. Chem. and Aers. News, April, 40
and the calculated parameters are listed in Table 1 as (1972).
well. From these results, the Era-Tab tablets manifested 3. E. J. Mendell, Manf. Chem. and Aers. News, June. 31
a satisfactory dissolution rate. (1972).
4. K. A. Khan and C. T. Rhodes, Pharm. Acta Helv., 51,
CONCLUSIONS 23 (1976).
5. P. P. Sanghvi, C. C. Collins, and A. J. Shukla, Pharm.
The modified rice starch, Era-Tab, exhibited good Res., 10, 1597 (1993).
flowability and made harder and less friable tablets than 6. Technical Information Sheet of Era-Tab, Erawan Phar-
Super-Tab Lactose, PPS, and Emcompress, except maceutical Research and Laboratory Co., Ltd., Thailand
Avicel PH-101. It was also shown that tablets with Era- (1994).
Tab as an excipient exhibited good disintegration and 7. C. E. Bos, G. K. Bolhuis. C. F. Lerk, and C. A . A.
dissolution properties. It is believed that Era-Tab will be Duineveld, Drug Dev. Ind. Pharm., 18, 93 (1992).
a possible alternative choice for direct compression ex- 8. R. L. Carr, Chem. Eng., 72, 163 (1965).
Drug Dev Ind Pharm Downloaded from informahealthcare.com by Mcgill University on 01/13/15

cipient in tablet formulation. 9. J. T. Fell and J. M. Newton, J . Pharm. Sci., 59, 688
(1970).
ACKNOWLEDGMENT 10. T. Pesonen and P. Paronen, Drug Dev. Ind. Pharm.,
12, 2091 (1986).
This research was supported by a grant from the 11. L. C. Tung, M.Sc. Thesis, Kaohsiung Medical College,
Cheng’s Pharmaceutical Sciences Foundation, Republic Taiwan, (1991).
of China. 12. R. W. Heckel, Trans. Metall. SOC.A.I.M.E., 221, 671
(1961).
REFERENCES 13. R. W. Heckel, Trans. Metall. Soc. A.I.M.E., 221, 1001
( 1961).
1. E. J . Mendell, Manf. Chem. and Aers. News, March, 14. J. A. Hersey and J. E. Rees, Nature, 230, 96 (1971).
For personal use only.

47 (1972). 15. F. Langenbucher, Pharm. Pharmacol., 24, 979 (1972).