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159
Dissolution test of low-dose acetylsalicylic acid tablets
Vol.18, No. 3, July - September 2009
Dissolution test of various low-dose acetylsalicylic acid preparations
marketed in Indonesia
Yeyet C. Sumirtapura,1 Arini Setiawati,2 Jessie S. Pamudji,1 Heni Rachmawati.1
1 School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia.
2 Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Abstrak
Tujuan Membandingkan profi l disolusi berbagai tablet asam asetilsalisilat dosis rendah salut enterik yang dipasarkan
di Indonesia.
Metode Studi disolusi dilakukan mengikuti Farmakope Amerika (USP)/Eropa, metode A, menggunakan alat 1 USP
(keranjang) 100 rpm, dengan 2 media: 0,1 N HCl, 120 menit untuk stadium asam, dan buffer fosfat pH 6,8, 90 menit untuk
stadium dapar. Sampel diambil pada 120 menit untuk stadium asam, dan setiap 10 menit sampai dengan 90 menit untuk
stadium dapar. Asam asetilsalisilat diukur kadarnya dengan spektrofotometer pada 280 nm untuk stadium asam, dan pada
265 nm untuk stadium dapar. Asam salisilat bebas diukur kadarnya hanya pada akhir stadium dapar dengan metode
HPLC. Ada 6 produk uji (Cardio Aspirin® 100 mg, Aptor® 100 mg, Ascardia® 80 mg, Thrombo Aspilet® 80 mg, Astika® 100
mg dan Farmasal® 100 mg), 3 batch untuk setiap produk, dan 6 unit untuk setiap batch.
Hasil Jumlah asam asetilsalisilat yang dilepaskan dari setiap produk asam asetilsalisilat yang diuji pada akhir stadium
asam (120 menit) berkisar dari 1,79% untuk Cardio Aspirin® sampai 6,92% untuk Thrombo Aspilet®, semua produk
memenuhi persyaratan farmakope sebagai produk salut enterik (< 10%). Jumlah asam salisilat yang diamati pada
akhir uji disolusi berkisar dari 3,47% untuk Cardio Aspirin® sampai 10,90% untuk Astika® dan 11,90% untuk Thrombo
Aspilet®. Thrombo Aspilet® menunjukkan sifat lepas lambat, yang menyebabkan variabilitas yang sedemikian tinggi dalam
melepaskan asam asetilsalisilat, sehingga salah satu dari 3 batch yang diuji tidak memenuhi persyaratan kompendial yaitu
lebih dari 75% (pelepasan hanya 55,11%). Variabilitas yang tinggi dalam melepaskan asam asetilsalisilat antar batch
juga ditemukan pada Farmasal® pada 10, 20, dan 30 menit dalam medium dapar. Dosis efektif asam asetilsalisilat terendah
sebagai obat antiplatelet untuk penggunaan jangka panjang adalah 75 mg asam asetilsalisilat sebagai tablet biasa, yang
ekivalen dengan 100 mg asam asetilsalisilat sebagai tablet salut enterik.
Kesimpulan Semua sediaan asam asetilsalisilat dosis rendah yang dipasarkan di Indonesia, merupakan produk salut
enterik, sedangkan Thrombo Aspilet® selain salut enterik juga merupakan produk lepas lambat. Cardio Aspirin®, diikuti
Aptor®, mempunyai dosis yang tepat untuk sediaan dosis rendah salut enterik (100 mg), konsisten dalam melepaskan asam
asetilsalisilat antar batch, dan paling stabil terhadap deasetilasi (inaktivasi antiplatelet). (Med J Indones 2009; 18: 159-64).
Abstrak
Aim To compare the dissolution profi les of various enteric-coated low-dose acetylsalicylic acid (ASA) tablets
marketed in Indonesia.
Methods The dissolution study was carried out according to US Pharmacocopoeiae (USP) /European Pharmacopoeiae,
method A, using USP apparatus 1 (basket) 100 rpm, with 2 media: 0.1 N HCl, 120 minutes for acid stage, and phosphate
buffer pH 6.8, 90 minutes for buffer stage. The sampling points were 120 minutes for the acid stage, and every 10 minutes
until 90 minutes for the buffer stage. The acetylsalicylic acid was assayed using spectrophotometry at 280 nm for the acid
stage, and at 265 nm for the buffer stage. The free salicylic acid was determined only at the end of the buffer stage with HPLC
method. There were 6 test products (Cardio Aspirin® 100 mg, Aptor® 100 mg, Ascardia® 80 mg, Thrombo Aspilet® 80 mg,
Astika® 100 mg and Farmasal® 100 mg), 3 batches for each product, and 6 units for each batch
Results The amount of ASA released from each ASA product tested at the end of acid stage (120 minutes) ranged from
1.79% for Cardio Aspirin® to 6.92% for Thrombo Aspilet®, all conformed to the compendial requirement for enteric-coated
product (< 10%). The amount of salicylic acid observed at the end of the dissolution test ranged from 3.47% for Cardio
Aspirin® to 10.90% for Astika® and 11.90 % for Thrombo Aspilet®. Thrombo Aspilet® showed sustained-release properties,
causing high variability in ASA release, such that one of the 3 batches tested did not fulfi ll the compendial requirement
of more than 75% (the release was only 55.11%). High variability in ASA release between batches was also found with
Farmasal® at 10, 20, and 30 minutes in buffer medium. The lowest effective dose of ASA as an antiplatelet drug for long-
term use is 75 mg of plain ASA, and this is equivalent to 100 mg of enteric-coated ASA.
Conclusions All of the low-dose ASA preparations marketed in Indonesia are enteric-coated products, while Thrombo
Aspilet® is not only an enteric-coated but also a sustained-release product. Cardio Aspirin®, followed by Aptor®, has
the right dose for low-dose enteric-coated preparation (100 mg), produces consistent ASA release between batches,
and the most stable towards deacetylation (antiplatelet inactivation). (Med J Indones 2009; 18: 159-64)
Key words: Dissolution profi le, enteric coated, deacetylation
160 Med J Indones
Sumirtapura et. al.
Low-dose acetylsalicylic acid (ASA) has been used
worldwide as an antiplatelet agent for prevention of
cardiovascular death, myocardial infraction, and stroke in
patients at high risk of occlusive vascular events.1 Among
various antiplatelet agents, ASA is the oldest, the cheapest,
and the most established, and therefore it becomes the
standard drug to which other antiplatelets are compared.1
Among the above-mentioned high risk patients, antiplatelet
therapy, especially acetylsalicylic acid (ASA), has been
found to reduce the combined outcome of any serious
vascular event by about one quarter, nonfatal myocardial
infarction by one third, nonfatal stroke by one quarter, and
vascular mortality by one sixth in a meta-analysis of >100
randomized trials.1 For this purpose, ASA has been used as
life-long secondary and primary prevention medication; the
most effective dose according to the meta-analysis is 75-
150 mg daily. The higher doses are less effective because
higher doses also block the synthesis of prostacyclin which
has platelet antiaggregation and vasodilator effects, while
the lower doses are reported to “spare” prostacyclin. Higher
doses also produce more gastrointestinal side effects
and have higher risks of major bleeding.2 To reduce the
gastrointestinal side effects, ASA is formulated as enteric-
coated tablets,3-5 which prevent the release of ASA in the
stomach, and thereby preventing its perfusion into gastric
mucosal cells which causes gastric injury.
The present study was conducted to compare the
dissolution profi les of various enteric-coated low-dose
ASA tablets marketed in Indonesia.
METHODS
Products tested
The products tested (3 batches for each product) were:
Cardio Aspirin® 100 mg tablet (Batch number/BN:
BXC7A91, BXBVUP2, BXC8EZ1), Aptor® 100 mg tablet
(BN: 2D1137B, 7B1030A, 611584), Ascardia® 80 mg
tablet (BN: B7G676G, B7C973F, B7G674G), Astika® 100
mg tablet (BN: 760306, 761203, 761216), Farmasal® 100
mg tablet (BN: TH 0921, PJ 0701, TC 0021), and Thrombo
Aspilets® 80 mg tablet (BN: 7032501, 6063102, 7032401).
All of the products were low-dose ASA that were produced
in Indonesia. These products were supplied by PT Bayer
Indonesia.
Instruments
The main instruments used were dissolution tester (United
States Pharmacopoeia/USP type)6 Erweka DT6, high
performance liquid chromatograph (HPLC) with variable
UV-Vis detector (HP 1100 series), spectrophotometer
Beckman DU 7500i, and pH-meter BeckmanTM 50.
Dissolution study
This study was conducted at School of Pharmacy,
Bandung Institute of Technology, Bandung, in the fi rst
quarter of 2008. There are two dissolution methods
for ASA that are used and accepted in Indonesia; one
of these methods is the method of USP/European
Pharmacopoeia.
The apparatus used was USP apparatus 1 (basket)6
100 rpm. The method was according to USP/European
Pharmacopoeia, method A,6,7 using 2 media: medium
1 was 0.1N HCl (pH=1), for acid stage, and medium
2 was phosphate buffer pH 6.8, for buffer stage. The
sampling time for acid stage was 120 minutes, while for
buffer stage were every 10 minutes until 90 minutes.
Spectrophotometry was used for the assay of ASA, at
280 nm for acid stage, and at 265 nm for buffer stage.
The free salicylic acid was determined only at the end
of buffer stage with HPLC method. There were 3 batches
for each product tested, and 6 units for each batch. These
batches and units were randomly taken from the market
(a pharmacy in Jakarta) by PT Bayer Indonesia.
Procedure6,7
Seven hundred fi fty mL of medium 1 (0.1 N HCl) was
transferred to the dissolution vessel and warmed to
370C (+ 0.50C). One tablet was placed in the basket, and
the basket was put in the dissolution vessel, the stirrer
was switched to 100 rpm and run for 120 minutes. Five
mL of the dissolution medium was taken as the fi rst
sample and the withdrawn dissolution medium was
replaced with the same quantity of medium 1. The
aspirin concentration in the sample was determined
spectrophotometrically at 280 nm.
Immediately after sampling and medium replacement
at the end of acid stage, 250 mL of medium 2 (0.20 M
tribasic sodium phosphate, previously heated to 370C)
was added. The pH was checked and was adjusted if
necessary to 6.8 + 0.05 with 2N HCl or 2N NaOH.
Five mL of the dissolution medium was withdrawn
regularly every 10 minutes until 90 minutes. Each
time of sampling, withdrawn medium was replaced
with the same quantity of the same medium. The
ASA concentrations in the samples were determined
spectrophotometrically at 265 nm (at which the
absorption is the same for both ASA and salicylic acid).
161
Dissolution test of low-dose acetylsalicylic acid tablets
Vol.18, No. 3, July - September 2009
Free salicylic acid concentration was determined only at
the end of buffer stage (90 minutes) with validated HPLC
method (with this method, the concentrations of ASA
and salicylic acid can be determined simultaneously).
The HPLC condition was as follows: the column was
SGE, Wakosil C-18, 250 x 4.6 mm, 5 μm; the mobile
phase was phosphate buffer-acetonitrile (60 : 40) pH 2.5,
1 mL/minute, with UV detector at 237 nm.
Estimation of drug dissolution rates
Drug dissolution rate was estimated during the main
dissolution phase (between 10% and 90% of drug
release)
Estimation of similarity factors
Similarity factor (f2) was estimated using time points
from 10 to 40 minutes. Those points were taken in
accordance to the general guideline in calculating
similarity factor (not more than one point that was
greater than 85%). The similarity factors would show
the similarity or the difference between the dissolution
profi les of the products tested.
Analytical methods
The analytical methods (spectrophotometric and HPLC
methods) were verifi ed for selectivity, linearity, and
precision. The selectivities of both methods were tested
for possible interference from dissolution medium, not
from tablet excipients since the excipients of each tablet
tested were not available
RESULTS
No interference was found from the dissolution
medium. The standard curve of ASA concentration
vs absorbance by spectrophotometric method in acid
medium was linear with R2= 0.9995, and that in buffer
medium was also linear with R2= 1. The standard curve
of salicylic acid concentration vs peak area by HPLC
method was linear with R2= 0.9996, and that of ASA
concentration was also linear with R2= 0.9999. The
precision of ASA assay by spectrophotometric method
in acid medium was high (coeffi cient of variation/CV=
0.70% and 1.25% for absorbance of 1 ppm and 4 ppm,
respectively); and that in buffer medium was also high
(CV= 1.09, 2.37, and 1.17% for absorbance of 0.5 ppm,
45 ppm, and 90 ppm, respectively). The precision of
salicylic acid assay by HPLC method was also high
(CV= 5.58, 3.54, and 2.88% for peak area of 1 ppm, 50
ppm, and 150 ppm, respectively)
Dissolution results
The results of the dissolution study of all ASA products
tested are presented in Table 1 and Figure 1.
Table 1. Amount ( in mg) of ASA dissolved from 6 products tested within 2 stages (mean + SD)
Time
(minute)
Acid medium
(0.1 N HCl) 120
Buffer medium
(pH 6.8)
0
10
20
30
40
50
60
70
80
90
1.79 + 1.47
(1.79%)
1.79 + 1.47
1.53 + 0.61
14.86 + 1.96
54.44 + 8.89
90.25 + 0.56
101.22 + 3.60
102.06 + 4.28
102.15 + 5.37
102.84 + 4.67
100.90 + 4.70
(100.90%)
3.70 + 1.11
(3.70%)
2.61 + 1.41
(3.26%)
5.53 + 3.00
(6.92%)
2.74 + 0.80
(2.74%)
3.25 + 1.71
(3.25%)
Product tested
Cardio Aspirin®
(100 mg)
Aptor®
(100 mg)
Ascardia®
(80 mg)
Thro.Aspilet®
(80 mg)
Astika®
(100 mg)
Farmasal®
(100 mg)
3.70 + 1.11
11.43 + 6.62
83.22 + 3.14
103.87 + 1.53
107.88 + 1.95
108.34 + 2.43
107.78 + 2.22
107.12 + 2.51
106.95 + 2.34
105.26 + 2.60
(105.26%)
2.61 + 1.41
48.38 + 13.57
86.46 + 4.70
92.62 + 1.31
91.94 + 1.38
90.87 + 0.58
89.81 + 0.44
89.08 + 0.50
88.92 + 0.97
88.02 + 1.26
(109.80%)
5.53 + 3.00
14.08 + 2.35
22.29 + 6.09
30.97 + 7.47
38.15 + 9.30
44.59 + 11.35
49.99 + 13.26
54.75 + 15.26
59.27 + 16.31
62.76 + 17.54
(78.46%)
2.74 + 0.80
12.13 + 2.90
65.93 + 5.00
93.87 + 0.34
100.05 + 1.83
100.24 + 2.46
99.70 + 1.45
99.64 + 1.73
99.13 + 1.71
98.81 + 2.80
(98.81%)
3.25 + 1.71
38.84 + 34.66
75.52 + 37.60
94.86 + 20.08
100.56 + 13.14
102.59 + 9.07
103.07 + 8.51
103.51 + 7.89
103.35 + 7.93
102.99 + 7.52
(102.99%)
162 Med J Indones
Sumirtapura et. al.
Acid resistance
According to the compendial requirement, less than
10% of ASA should be released from enteric-coated
formulations after 120 minutes in acid medium.
The amount of ASA release from each ASA product
that was tested at the end of acid stage (120 minutes)
can be seen in Table 1, and these were less than 10% of
the stated potencies. Therefore, all of the tested drugs
conformed to the compendial requirement for enteric-
coated product. Cardio Aspirin® tablet released the
smallest amount of ASA during the acid stage, less than
2% of ASA (1.79%) were released after 120 minutes of
dissolution in acid medium. Meanwhile, the other drug
products released more ASA which varied from 2.74%
Figure 1. Dissolution profi les of ASA from different ASA products tested in buffer medium (pH 6.8)
to 6.92%, but the differences were not signifi cant.
Dissolution profi les in buffer stage
The results showed that the 6 ASA products had different
drug release profi les. In buffer medium, ASA was
released immediately from Ascardia® and Farmasal®
tablets, but there was a lag time of about 10 minutes
for Aptor® and Astika® tablets, and a longer lag time of
about 20 minutes for Cardio Aspirin® tablet, which then
fastly released ASA after 20 minutes of dissolution (see
Figure 1).
A very different release profi le was observed for
Thrombo Aspilet® tablet, which showed sustained or
slow release properties (see Figure 1).
0
25
50
75
100
125
010 20 30 40 50 60 70 80 90
Time (minutes)
Cardio Aspirin 100 mg
A
ptor 100 mg
A
scardia 80 mg
Thrombo Aspilet 80 mg
A
stika 100 mg
Farmasal 100 mg
mg of ASA dissolved
mg of ASA dissolved
125
0
25
50
75
100
Cardio Aspirin 100 mg
Aptor 100 mg
Ascardia 80 mg
Thrombo Aspilet 80 mg
Astika 100 mg
Farmasal 100 mg
Time (minutes)
0 10 20 30 40 50 60 70 80 90
Table 2. Amount (in %) of ASA released at 90 minutes in buffer stage
Batch
Tested product
Cardio Aspirin
(100 mg)
Aptor
(100 mg)
Ascardia
(100 mg)
Th.Aspilet
(100 mg)
Astika
(100 mg)
Farmasal
(100 mg)
1 105.95 106.92 108.88 98.62 100.32 106.20
2 96.67 106.61 111.82 55.11 100.53 108.38
3 100.09 102.27 108.69 81.63 95.57 94.41
Mean 100.90 105.26 109.80 78.46 98.81 102.99
163
Dissolution test of low-dose acetylsalicylic acid tablets
Vol.18, No. 3, July - September 2009
DISCUSSION
All the investigated low-dose ASA products in this study
were enteric-coated formulations, and all of the products
conformed to the compendial requirement of releasing
ASA less than 10% after 120 minutes in acid medium.
Cardio Aspirin® tablet released the lowest amount of
ASA (less than 2%), which suggested that it was the
most acid resistant compared to the other products (see
Table 1), but the differences were not signifi cant.
As enteric-coated products, the ASA should be released
in buffer medium, and the compendial requirement re-
quires that more than 75% of ASA should be released
in 90 minutes. Again, our data showed that all of the
products fulfi lled this requirement, except Thrombo As-
pilet®, as one of the 3 tested batches released ASA only
55% at the end of the dissolution test (see Table 2).
Enteric-coated low-dose ASA has been shown to have
less antiplatelet activity compared to equivalent doses
of plain ASA.8 Lower bioavailability of these prepara-
tions and poor absorption from the higher pH environ-
ment of the small intestine may result in inadequate
platelet inhibition. Enteric-coated ASA preparations
release ASA into the upper small intestine, which has a
near neutral pH, causing ASA to become unstable and
some are deacetylated to salicylic acid. Deacetylation
of ASA to salicylic acid causes ASA to lose its activity
to acetylate serine 529 at Cox-1 enzyme, which produc-
es irreversible inhibition of the enzyme in platelet, and
thereby causes persistent antiplatelet effect. Therefore,
deacetylation causes inactivation of ASA in producing
persistent antiplatelet effect
Enteric-coated preparations may also differ in their
rate of dissolution at the intestinal pH (pH = 6). Fur-
thermore, enteric-coated 75 mg ASA preparation was
estimated to deliver a dose equivalent to 50 mg plain
ASA.8 This may be true for enteric-coated 80 mg ASA
preparations as was shown in the present study for As-
cardia® and Thrombo Aspilet®. To ensure adequate in-
hibition of thromboxane production, plain 75 mg ASA
or an equivalent dose of enteric-coated ASA (estimated
to be around 100 mg) should be used.8 The most effec-
tive dose of ASA as an antiplatelet drug for long-term
use is 75 to 150 mg.1 Since the side effects of ASA is
dose-dependent,2 then 75 mg of plain ASA would be the
right choice, and this is equivalent to 100 mg of enteric-
coated ASA.8
Farmasal® is an enteric-coated 100 mg ASA prepara-
tion, but it had a very high variability in ASA release
between batches, especially at 10, 20, and 30 minutes
in buffer medium (the standard deviations were more
than 20%) (see Table 1), which might indicate incon-
sistency in the manufacturing process.
Cardio Aspirin®, Aptor®, and Astika® are 100 mg en-
teric-coated tablets, and have shown low variabilities
of ASA release between batches (Table 1). Aptor® and
Astika® had a lag time of about 10 minutes, while Car-
dio Aspirin® had a lag time of about 20 minutes, before
ASA was fastly released afterwards. These facts indi-
cated that the tablets of Aptor® and Astika® required
10 minutes, while Cardio Aspirin® tablet required 20
minutes to dissolve at the near neutral pH of the small
intestine. However, Astika® showed a high variability in
producing salicylic acid compared to Aptor® and Cardio
All of the products tested released more than 75% of ASA
in 90 minutes of dissolution (compendial requirement),
except for one of the 3 batches of Thrombo Aspilet®
which showed less than 75% of drug released in 90
minutes (see Table 2).
Free salicylic acid
At the end of dissolution test (90 minutes of ASA in
buffer phase), the amount of salicylic acid release from
ASA was measured. Deacetylation of ASA to salicylic
acid causes ASA to lose its activity to acetylate COX-1
enzyme and to produce persistent antiplatelet effect.
The results of salicylic acid assay at the end of dissolu-
tion test are presented in Table 3. The amount of sali-
cylic acid found during the dissolution test was smallest
with Cardio Aspirin® tablet, followed by Aptor® tablet,
Farmasal,® Ascardia®, Astika® and Thrombo Aspilet®.
Table 3. The amount of salicylic acid (in %*) observed at the end of the dissolution test
Tested product
Cardio Aspirin
(100 mg)
Aptor
(100 mg)
Ascardia
(80 mg)
Th. Aspilet
(80 mg)
Astika
(100 mg)
Farmasal
(100 mg)
Mean 3.47 4.72 6.25 11.90 10.90 5.73
SD 0.85 0.51 0.93 5.36 3.94 1.49
Range 1.60 – 4.59 4.18 – 5.62 5.20 – 7.69 7.31 – 25.51 7.04 – 16.84 1.40 – 7.77
*of total ASA content
164 Med J Indones
Sumirtapura et. al.
Aspirin® at the end of buffer stage (see Table 3), which
indicated that it was more unstable in intestinal pH com-
pared to Aptor® and Cardio Aspirin®. Therefore, among
these 3 enteric-coated tablets that contain 100 mg ASA,
Cardio Aspirin® and Aptor® were the most stable to-
wards deacetylation, and produced the lowest amount
of salicylic acid at the end of buffer stage (90 minutes),
as shown in Table 3.
Our data also showed that Thrombo Aspilet® had both enter-
ic-coated and sustained-release properties. This sustained-
release ASA preparation produced more salicylic acid (see
Table 3), may be because it released ASA steadily but in
small amounts, and therefore more prone to deacetylation.
This instability towards deacetylation was shown in the
high variability in producing salicylic acid at the end of the
dissolution test, as shown in Table 3. As already mentioned,
Thrombo Aspilet® also showed a high variability between
batches in ASA release at 90 minutes in buffer stage (see
Table 2). These results were in accordance with the study
of Dooley et al,9 which showed that the slow-release 75 mg
ASA was worse in terms of variation in platelet aggregation
and serum TXB2 levels in healthy volunteers. Consequent-
ly, sustained-release critically low doses of ASA may result
in subtherapeutic effects.9
Enteric-coated ASA may cause rectal bleeding, ulceration
of ascending colon, collageneous colitis, and diverticular
bleeding from a duration of use ranging from 18 days to
15 years.10 However, enteric-coated ASA 100 mg/day
caused signifi cantly less gastroduodenal damage than the
same dose of plain ASA.4 This is due to enteric-coated
ASA that released ASA mainly in the intestine, therefore
decreased ulcerogenicity in the upper gastroduodenum
and shifted the site of damage to the more distal intes-
tine.10 Moreover, the sustained-release preparations, due
to the sustained release of the drug and its longer presence
within the intestinal tract, induced more local damage in
the distal intestinal wall in addition to the systemic intes-
tinal effect.10-12 This fact was due to a signifi cant increase
in the permeability of the lower intestine produced by the
sustained-release formulations, but not of the gastroduo-
denum, while the immediate-release products signifi cantly
increased the permeability at the gastroduodenal level.11,12
Nevertheless, the gastrointestinal blood loss with enteric-
coated ASA was less compared to that with plain ASA,
but more compared with control,13 which implies that the
gastric contribution to gastrointestinal ASA induced blood
loss may be more important than the contribution of the
small intestine.13 This reduced GI blood loss with enteric-
coated ASA was accompanied by decreased gastroduode-
nal mucosal damage compared with plain ASA, as mea-
sured endoscopically and symptomatically.14
In short, sustained-release low-dose ASA showed high
variability in ASA release between batches and in pro-
ducing salicylic acid (deacetylation) at the end of the
dissolution test, and therefore may be less effective in
inhibiting platelet aggregation. It may also cause more
local damage in the distal intestine.
In conclusion, all of the investigated low-dose ASA
products in this study are enteric-coated formulations and
are marketed in Indonesia. Thrombo Aspilet® besides an
enteric-coated is also a sustained-release product. Cardio
Aspirin®, followed by Aptor®, has the right dose for low-
dose enteric-coated preparation (100 mg), produces con-
sistent ASA release between batches, and the most stable
towards deacetylation (antiplatelet inactivation).
Acknowledgment
We thank PT Bayer Indonesia for funding the study.
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