GULF MEDICAL JOURNAL
GMJ, ASM 2013;2(S2):S99-S106
Acid neutralization capacity and cost effectiveness of
antacids sold across various retail pharmacies in United
Arab Emirates
Shery J*, Annie S, Shijna A, Reham K, Mariyam I
College of Pharmacy, Gulf Medical University, Ajman, UAE
*Presenting Author
ABSTRACT
Objective: To determine and verify the acid neutralization capacity (ANC) of antacid
preparations sold across various retail pharmacies in UAE. Another important objective is to
quantify the amount of sodium, calorific content, overall monthly consumption and cost of
therapy with respect to its composition and manufacturer.
Materials and Methods: In Vitro analysis was carried out on various antacid formulations as
per USP30/NF25 methodology at 37±30C.
Results and Conclusion: The tablet and liquid antacids fall into four statistically different
ANC groups. The standard deviation for the lot to lot variation of tablet antacids was estimated
to be 0.42. Three of them (H-1, H-2, H-3 and H-4) have ANCs that correlate with liquid antacid
medications mentioned in high ANC class. Out of the five liquid antacids tested, only two
found (LH-1 and LH-2) to have high ANC between four lots at 5% level of significance. The
ANC of the maximum effective liquid antacid was proven to be twice strong, when compared
to the lowest. This variation in capacity for neutralization is not observed, on the product
description of antacid brands. The standard dose one to two teaspoonfuls will neutralize
20.22/40.44 mEq to 35.92/71.84mEq, depending on the antacid selected. The normal single
dose needed to neutralize the maximum low/high dose regimen by liquid antacids and tablet
antacids were estimated. It was apparent from quantification that high or an intermediate
high ANC group contributes maximum ANC with minimum dosage volume/weight ratio.
Consumption of these categories of antacids benefits in less sodium and calorie intake and
minimum expenditure to pharmacist/community. Monthly cost of high dose therapy per day
for high ANC tablet antacids is much cheaper than low ANC tablet antacids. In conclusion, if
antacid doses to be used judiciously, it is imperative that acid neutralization capacity (mEq)
should be enclosed on product label.
Keywords: antacids, acid neutralization capacity, milliequivalent, sodium, calorific value, cost
effectiveness
INTRODUCTION
Antacids have been the pillar of gastric
ulcer therapeutics. Several controlled
studies have established their efficacy
in improving the curing of peptic and
duodenal
ulceration1.
Despite
the
competition provided by new H2 receptor
blockers, antacids are still being
prescribed in large quantities. Many
antacids preparations are available in
the market and are often reformulated by
the manufacturers. Physicians and also
public are therefore often bewildered by
the wide choice of such over the counter
(OTC) preparations and by the conflicting
advertisements extolling the merits of one
preparation over the other.
Ideally, a prescribing physician should
take into consideration the following when
choosing an antacid preparations with the
following considerations; It should have
maximal acid neutralizing capacity (ANC)
expressed in mEq (milli equivalent); it
should neutralize the greatest amount of
acid per unit cost; and it should be both
palatable and conveniently consumed
by the patient. Other factors should be
considered include the sodium content
of the antacid, calorific contents, its
constipating or diarrheogenic effects, and
its physical (tablet or liquid) form and
price to the pharmacist2.
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RATIONALE
Antacids are frequently used selfprescribed
over-the-counter
(OTC)
medication. It consists of calcium
carbonate, and different forms and
combinations
of
magnesium
and
aluminum salts. The action of antacid
on stomach is as the result of active
neutralization of gastric HCl and inhibiting
pepsin4.Typically, large doses of antacids
are required to elevate gastric pH notably
and ANC of antacid preparations may vary
largely between different brands. Since
the effectiveness of antacid preparation
is based on ANC, the cost of the antacid
preparations should be ideally based on
targeted neutralizing capacity.
Globally, and also in the UAE, past
10 years have witnessed many changes
in antacid formulations3. Although the
variability in acid neutralizing capacity
of the antacid formulations has been
narrowed down from a sevenfold in the
1970’s down to a threefold difference in
the 1980’s, no study has been carried in
the UAE to evaluate the neutralization
capacity of currently marketed antacid
formulations. As the efficacy of antacids
is associated to its ANC, it is hence
essential
to
differentiate
presently
marketed antacid products. What is also
noteworthy is the fact that the antacid
product label never incorporate any data
on ANC. Many antacid preparations
with its actives, excipients, flavoring
agent and sweetening agent may contain
considerable amount of sodium and
calorie. Therefore it is important to choose
an antacid formulation with sodium and
calorie restrictions for patients suffering
from hypertension, renal impiairement,
diabetes etc5.
Hence our aims to determine and
verify the ANC of antacid preparations
sold across various retail pharmacies
in the UAE and in addition to quantify
the amount of sodium, calorific content,
overall monthly consumption and cost of
therapy with respect to its composition
and manufacturer.
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OBJECTIVES
1. Evaluation of acid neutralizing
capacity
of
various
antacid
preparations both liquid and solid
form.
2. Calculation of the nutritional value
and sodium content of antacid
preparations.
3. Evaluation of the monthly dose
equivalent to target neutralizing
capacity of 140 mEq as well as
monthly cost of therapy.
4. To detail the composition with its
manufacturer of each marketed
antacid preparations.
Conceptual/operational definitions:
1. Acid neutralizing capacity (ANC)
of an antacid is a measure of an
antacid tablet or liquid formulation’s
ability to buffer against stomach
acid at a temperature of 37±20C
expressed in mEq.
2. Milliequivalent (mEq) is defined as
gram equivalent expressed in one
thousandth of a chemical element,
an ion, a radical, or a compound.
Table 1: ANOVA of 10 tablets antacids (ANCs),
each estimated in triplicate and in four lots
Degrees of
Variable
Mean square F
freedom
Tablet
9
65.8
659
Error
12
0.118
Table 2: ANOVA of 5 liquid antacids (ANCs), each
estimated in triplicate and in five lots
Degrees of
Mean
Liquid
Lots
freedom
4
10
square
65.8
1.56
Error
98
0.0231
Variable
F
143
23
-
Table 3: ANOVA of 5 liquid antacids (lot average
ANCs)
Variable
Degrees of
Mean
freedom
square
12
65.4
112
23
0.80
-
F
Liquids
lot
means
Error
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GMJ, ASM 2013;2(S2):S99-S106
Table 4: Attributes of 10 solid antacids
Ingredients
ANC (mEq/
tablet)
Na+
content (mg/
tablet)
Calorie
content
(mg/tablet)
Average price
per one strip
(10 tablets)
AED
Al(OH)3- 200 mg
Mg(OH)2- 200 mg
34.88
0.9
2.8
4.375
H-2
CaCO3-500 mg
31.74
0
0
4.285
H-3
Al(OH)3- 200 mg
Mg(OH)2- 200 mg
33.00
1.2
2.4
2.0
H-4
CaCO3-1000 mg
31.27
0
5
4.5
29.65
0.8
2.5
8.125
26.97
14.0
1.5
1.8
20.12
1.2
2
2
18.89
15.42
2.5
1.5
19.13
5
2.4
1.6
19.42
1.4
2.4
1.8
ANC group;
Product
High
H-1
IntermediateHigh
IH-1
IH-2
Al(OH)3- 160 mg
Mg(OH)2- 105 mg
Al(OH)3- 680 mg
MgCO3- 80 mg
Intermediate
I-1
Al(OH)3- 405 mg
Mg(OH)2- 100 mg
Low
L-1
L-2
L-3
Al(OH)3- 225 mg
Mg(OH)2- 200 mg
Al(OH)3- 250 mg
Mg trisilicate120mg
Mg(OH)2- 120mg
Al(OH)3- 225 mg
Mg(OH)2- 200 mg
Table 5: Attributes of 5 liquid antacids
Ingredients
(5ml)
ANC
(mEq/5ml)
Sodium
content
(mg/5ml)
Calorie
content
(mg/5ml)
Average
price per 10
ml(AED)
LH-1
Al(OH)3-225mg
Mg(OH)2- 200mg
35.83
1.4
1.6
0.5
LH-2
Al(OH)3-215mg
Mg(OH)2- 80mg
35.92
0.9
2.2
0.55
Sodium Alginate-250mg
Sodium Bicarbonates133.5mg
CaCO3- 80mg
30.26
1.1
1.4
0.55
Al(OH)3- 405 mg
Mg(OH)2- 100 mg
20.22
1.2
2.2
0.475
Al(OH)3-250 mg
Magnesium trisilicate120 mg
Mg(OH)2-120mg
18.22
5
2.4
1
ANC Group;
Product
HIGH
INTERMEDIATE HIGH
LIH-1
INTERMEDIATE
LI-1
LOW
LL-1
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GMJ, ASM 2013;2(S2):S99-S106
Table 6: Comparative evaluation of liquid/solid antacids belong to different ANC group
Single dose tab/
volume(ml)/day
ANC group
Product
80mEq
144mEq
Daily sodium
intake(mg)
80mEq
144
mEq
Daily calorie
intake(mg)
80mEq
Price pharmacist
(AED)
144
mEq
80
mEq
144
mEq
Monthly
cost of
high
dose
therapy
(AED)
ANC Group- Tablet
i)H-1
3 Tab
5 Tab
2.7
4.5
2.0
3.6
1.31
2.19
65.7
ii)H-2
3 Tab
5 Tab
NA
NA
NA
NA
1.29
2.15
64.5
iii) H-3
3 Tab
5 Tab
2.4
4.3
2.2
4.0
0.6
1.00
30.00
i)IH-1
3Tab
5 Tab
2.4
4
1.8
3.2
2.44
4.06
121.8
ii)IH-2
3 Tab
6 Tab
1.8
3.2
1.1
1.98
0.55
1.11
Intermediate
i)I-1
4 Tab
8 Tab
2.4
4.3
1.0
1.2
0.8
1.60
48.00
Low
i) L-1
6 Tab
10 Tab
1.1
2.0
1.6
3.0
0.9
1.50
45.00
6 mL
1.8
3.2
2.4
4.3
0.15
0.33
9.9
6 mL
2.2
4.0
2.4
4.0
0.17
0.33
9.9
High
Intermediate
high
33.33
ANC Group –Liquid
High
Intermediate
high
Intermediate
Low
i)LH-1
ii) LH-2
iii) LH-3
3 mL
3 mL
LIH-1
3 mL
6 mL
1.6
2.88
2.0
3.6
0.17
0.33
9.9
LI-1
4 mL
7 mL
2.4
4.3
1.0
1.2
0.19
0.34
10.2
LL-1
5 mL
9 mL
1.8
3.24
1.5
2.7
0.2
0.90
27.00
Figure 1: Classification of tablet antacids
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GMJ, ASM 2013;2(S2):S99-S106
Figure 2: Classification of liquid antacids
Figure 3: Liquid Antacids/Solid Antacids: ANC and Average Price for High Dose Therapy/Day
Figure 4: Solid Antacids: ANC and Average Price for High Dose Therapy/Day
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Figure 5: Liquid Antacids: ANC and Average Price
for High Dose Therapy/Day
Figure 6: Liquid Antacids, Tablet antacids and
Monthly Cost of High Dose Therapy
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MATERIALS AND METHODS
The ANC of 10 solid/5 liquid antacids,
purchased from community pharmacies
in the Ajman area of UAE, was analyzed
in triplicate with the “USP-XX-NF-XV”
acid neutralization test as follows.
Methodology:
In Vitro Acid Neutralizing Capacity
USP:
The acid neutralizing capacity was carried
out as per USP30/NF256,7. In short, all
tests were conducted at a temperature
37±30C.A pH meter was standardized
using
potassium
biphthalate
and
potassium tetraoxalate (0.05 M each)
standardized
buffers
respectively.
Magnetic stirrer was used to maintain
a stirring rate of 300±30 RPM.Average
tablet weight was determined from 20
tablets. The tablets were size reduced to
a fine powder form and accurate amount
equal to minimum dose was transferred
to a 250 mL beaker. This 5 mL of alcohol
was added and mixed to wet the sample
intensely. To this mixture 70 mL of water
was added for no chewable and 50 mL for
chewable tablet, and then it was mixed on
a magnetic stirrer for a period of 1 minute.
30 mL of 1 N HCl was added and stirred
accurately for 15 minutes. The titration
was carried out immediately to determine
the excess HCl using 0.5 N NaOH so as
to attain a stable pH (= 3.5).The number
of milliequivalent of acid used up was
calculated by the equation as follows:
Total mEq = (30 X NHCl) (VNaOH X NNaOH).
In which NHCl and NNaOH are the
normalities of the HCl and the NaOH,
respectively and VNaOH is the volume of
NaOH used for titration. The results were
expressed as total mEq per g of substance
(USP). We have received the sodium and
calorie contents of the respective antacids
from the manufacturers.
RESULTS
Tablet antacids
Different lots were not accessible for
the ten (10) tablet antacids tested. The
results of ANOVA of the actual ANCs are
shown in Table 1.The S.D for the within-
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lot replication failure was estimated as
0.42.The tablet antacids can be classified
into three ANC groups (Table 4 & Figure
1) Three of them (Maalox plus,Chooz and
Moxal plus) have ANCs that conform with
those of liquid antacids in the high group.
There is statistical data that three tablet
antacids with lowest ANC are higher than
ANC of 7 other antacid tablets as long as
the standard deviation of the lot-to-lot
variation does not exceed 2.35.
Sodium and calorie contents and cost
to the public/pharmacist
The Na+ and calorie contents and price to
the pharmacist of the antacids we tested
is given in Table 4.
Liquid antacids
Five liquid antacids tested are analyzed
for ANC within the lot for reproducibility
(Fig 2).Only two (Maalox plus and Moxal
plus) found to have high ANC between 4
lots at the 5% level of significance. The
ANOVA of 5 products are shown in Table 2
and Table 3. Liquid antacids are classified
into 4 statistically different groups based
on acid neutralization capacity (Table
5 and Figure 2). All groups showed no
correlation of ANC to the total amount
of antacid ingredients. From statistical
analysis, we estimated that SD= 0.23; lotlot error=0.92, =single observation error=
0.95; lot mean error=0.93.
DISCUSSION
The acid neutralization capacity of most
effective liquid antacid analyzed was
twice that of least effective. The variation
in neutralize capacity was not observed
in any one product label of antacid
brands. Undoubtedly, the actual ANC
was not shown on the label of all product
manufacturers. Most companies advocate
a regular dose of 1-2 teaspoonfuls (5-10
ml) of antacid, disregarding of product’s
ANC. The dose may neutralize 18.22
mEq/5 ml to 35.83 mEq/5 ml or 36.44
mEq/5 ml to 71.66 mEq/10 ml of acid,
calculating based on preferred anatacids.
Due to this large deviation in neutralizing
capability, the brand and dose must be
established when antacid administration
GMJ, ASM 2013;2(S2):S99-S106
is being suggested or recommended.
There was no variation in ANCs
found between each of the three groups
of liquid antacids tested statistically.
Table 6 shows average normal single dose
necessary to neutralize 80 and 144 mEq
of acid with respect to three batches of
liquid antacids and tablet antacids. The
doses selected represents maximum low
/ high dose antacid regimen. It is evident
from the table that high / intermediate
high ANC (liquid and tablet) contribute
maximum acid neutralization with lowest
dose volume/weight. The consumption
of these antacids also allows minimum
sodium and calorie intake and cost to the
pharmacist. Before selection of an antacid
product for those patients with restriction
on their sodium and calorie intake, it
is necessary to investigate sodium and
calorie contents.
Liquid antacids compared to tablet
antacids have been endorsed in the
treatment of gastric ulcer condition due to
greater surface area, which is responsible
for their excellent neutralization capacity.
Nevertheless, three of the tablet antacids
analyzed found to have ANCs that are
comparable to those of higher ANC liquid
antacids and higher than the lower ANC
group. These tablet antacids contains
nearly identical amount of ingredients as
higher ANC liquid antacid group. As well,
these tablets are designed to dissolve
freely, a vital aspect in quantifying the
ANC of a tablet.
Tablet antacids are cheap, acceptable,
portable and handy than liquid antacids,
therefore afford as feasible substitute when
doses to be taken outdoor. For example,3
to5 tablets of Maalox plus, Chooz and
Moxal plus would need to be taken to
cater an ANC of eight to one hundred
and forty four mEq. It is suggested that
chewable tablet antacids can increase
surface area and therefore yield superior
neutralization capacity. All the liquid and
tablet antacids tested provide < 1 mEq of
sodium.
Monthly cost of large dose therapy for
high ANC tablet antacid is much cheaper
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than low ANC tablet antacid (Fig 3 and Fig
4).Liquid antacids monthly dose therapy
is one by third of cheapest tablet antacid
therapy (Fig 5).Sodium content and
calorific value of all antacids are negligible
due to availability of non-calorific and
non-sodium containing excipients.
CONCLUSIONS
When
large
dose
antacids
are
recommended for the treatment of
gastric ulcers, antacids with high acid
neutralization capacity are the most
preferred agents. These products can
contribute highest neutralization capacity
with minimum dose volume/weight ratio,
sodium, calorie contents, and price to the
pharmacist/public.
Due to high neutralization capacity,
portability and acceptability, few tablet
antacids can be substituted for liquid
antacids. It is impractical to foresee inter
lot difference within liquid and tablet
antacids, but may aid in demonstrating
an unusual change in the effectiveness of
the antacid products.
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Conclusively,
antacids
can
be
consumed judiciously provided ANC
details are enclosed on the label of these
products.
REFERENCES
1. Hollander D, Harlan J. Antacids vs placebos
in peptic ulcer therapy; a controlled doubleblind investigation. JAMA. 1973;226:81-5.
2. Drake D, Hollander D. Neutralizing capacity
and cost effectiveness of antacids. Ann Intern
Med. 1981;94:215-217.
3. Peterson WL, Sturdevans R, Frank HD.
Healing of dueodenal ulcer with an antacid
regimen. N.Engl J Med. 1977;297:341-5.
4. Paul NM, Michael EB. Antacids Revisted: A
review of their clinical pharmacology and
recommended therapeutic use. Drugs.
1999;57:855-870.
5. Baker LL, Canik CA.Antacids:relevant
considerations for the pharmacist. Wis
Pharm. 1980;49:206-208,211.
6. United States Pharmacopoeia- XXX/National
Formulary-XX1X.US
Pharmacopoeial
Convention, Rockville, Md. Acid Neutralizing
Capacity.301. 2007.
7. Antacid drug products for over-the-counter
human use; Proposed amendment of antacid
monograph. Federal Register; Department of
health and Human Services, FDA, 58(183).
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