DETERMINATION OF ACID NEUTRALIZING CAPACITY OF

VARIOUS MARKETED ANTACIDS IN NEPAL

IN PARTIAL FULFILLMENT OF REQUIREMENT FOR DEGREE OF BACHELOR

OF PHARMACY
BY
SHIVA ARYAL
A DISSERTATION SUBMITTED TO THE
TRIBHUVAN UNIVERSITY
 OVERVIEW

Introduction
Rationality of Study
Literature Review
Objectives
Materials and Methods
Results and Discussion
Conclusion
Reference
 1.INTRODUCTION
• Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1.5 to 3.5 and is
composed of 0.5 % hydrochloric acid (HCl).
• Other cells in the stomach produce bicarbonate to buffer the acid, ensuring the pH does not
drop too low (acid reduces pH). Also cells in the beginning of the small intestine, or
duodenum, produce large amounts of bicarbonate to completely neutralize any gastric acid
that passes further down into the digestive tract.
• However, sometimes the stomach begins to secrete an excess of HCl. This leads to a
condition known as Gastric Hyperacidity. This condition can also be triggered by the intake
of too much food or highly spiced food. This, in turn, makes the stomach lining cells to
secrete more acid resulting in Hyperacidity.
• To counter this situation, antacids have been developed. Antacids are commercial products
that neutralize the excess acid in the stomach providing a sensation of relief to the person.
The action of antacids is based on the fact that a base can neutralize an acid forming salt
and water.[1]
 Working of Antacids

• If the antacid contains NaHCO3 then the reactions that occur in the stomach are:

• The excess Na+ and HCO3- ions are absorbed by the walls of the small intestines as the
food passes through.
• The H2CO3 formed during the reaction decomposes rapidly to form water and carbon
dioxide gas.[2]
• Types of Antacids
• Sodium Antacids: Sodium bicarbonate (commonly known as baking soda) is
perhaps the best-known of the sodium-containing antacids. It is potent and fast-
acting. As its name suggests, it is high in sodium. If you're on a salt-restricted diet,
and especially if the diet is intended to treat high blood pressure (hypertension),
take a sodium-containing antacid only under a doctor's orders.
• Magnesium Antacids: Magnesium salts come in many forms -- carbonate,
glycinate, hydroxide, oxide, trisilicate, and aluminosilicate. Magnesium has a mild
laxative effect; it can cause diarrhea.
• Calcium Antacids: Antacids in the form of calcium carbonate and calcium
phosphate are also potent and fast acting. Regular or heavy doses of calcium
(more than five or six times per week) can cause constipation. Heavy and
extended use of this product may clog your kidneys and cut down the amount of
blood they can process. [2]
Determination of concentrations of substances in neutralization

• The experimental method about neutralization is the acid-base titration.

• An acid- base titration is a method that allows quantitative analysis of the concentration of
an unknown acid or base solution.
• Before starting the titration a suitable pH indicator must be chosen. In this project, Methyl
orange is chosen. The endpoint of the reaction is the point at which all the reactants have
reacted.
• Methyl orange is used to determine the end point of the titration which indicates complete
neutralization. In the presence of methyl orange an acid solution is red in colour and the
basic solution is yellow.
• By keeping track of exactly how much NaOH is needed to complete the neutralization
process, the amount of HCl originally neutralized by the antacid can be calculated. The
difference between the number of moles of HCl initially added to the antacid and the number
of moles of HCl neutralized by the NaOH during the titration is the number of moles
neutralized by the antacid.[9]
 2. RATIONALITY OF STUDY
• Antacids are frequently used self prescribed 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 pepsin. 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, past years have
witnessed many changes in antacid formulations, not many studies has been
carried out in Nepal 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. So, the aim of
this study is to evaluate the extent of acid neutralization capacity of different
formulations available in the Nepalese market and to help pharmacists and
practicing physicians to choose the best formulation among a very large number
 3. LITERATURE REVIEW
•Abdu et.al carried out evaluation of neutralizing capacity of 5 different commercial brands of
antacid tablets of which Gaviscon showed highest ANC of about 82.6% and ranitidine with lowest
of 36.6%.
•Katakam et.al carried out comparative study of the acid neutralizing capacity of commercially
available antacid formulations (suspension, chewable tablet and effervescent powder) in Libya
which showed that magaldrate containing antacid (Sedo-Mag suspension) had highest ANC with
28.90mEq per dose based on daily dose of 280mEq of antacid. This indicated that suspension
formulations possessed better ANC compared to other dosage form.
•MacCara et.al studied ANC of 23 liquid antacids and 18 tablets commercially available in Canada.
The study showed that 6 tablets (Amphojel, Amphojel plus, Camalox, Gelusil-400, Maalox and
mylanta-2) and 5 concentrated liquid formulation (Mylanta-2 extra strength, Amphojel 500,
Gelusil extra strength, Malox TC and Diovol Ex) had higher ANC than the rest.
Contd…
• Malviya et.al carried out evaluation of acid neutralizing capacity of
marketed Digene tablet in which the acid neutralizing capacity of
Digene tablets was found to be 0.20019 mol.
• Jagadesh et.al carried out the study of acid neutralizing capacity of
various antacid formulations in which the acid neutralizing capacity
among the liquid formulations was highest for Dioval 26.28±0.05 by
pH meter method and 26.17±0.18 by titration method. Among solid
antacid formulations ANC was highest with Riflux forte being
25.77±0.06 by pH meter method and 25.73±0.17 by titration method.
 4. OBJECTIVES

General Objectives:
To determine acid neutralizing capacity of various marketed antacids in Nepal.
Specific Objectives:
1. To determine the acid neutralizing capacity of various marketed antacids by
titration and pH meter method.
2. To help pharmacists and practicing physicians to choose the best drug among a
very large number of formulations.
 5. MATERIALS AND METHODS

5.1 Materials

a. Materials required
I. Sample
•Marketed Antacids (2 batches each)
II. Chemicals
•1N HCL
•0.5N NaOH
•Methyl orange
•Phenolpthalein
Contd…
b. Equipments and Instruments Required
• Electronic Balance, d=0.0001 g, Max=110g, model: Adventurer Pro AU114 (Ohaus
Corporation Pine Brook, NJUSA)
• Beaker
• Burette
• Mortar and pestle
• Conical flask
• pH meter, model: CL180 (Labline Technology)
• Magnetic Stirrer
• Filter paper (Whatman)
 5.2 Methodology
• Preparation of 1N HCL: 85 ml of hydrochloric acid was diluted with water to produce
1000ml.
• Standardization of 1N HCL: 1.5 g of anhydrous sodium carbonate which was previously
heated at about 270°C for 1 hour was accurately weighed and dissolved in 100 ml of water. 0.2
ml of methyl red solution was added followed by slow addition of acid with constant stirring
until the solution became faintly pink. The solution was heated to boiling. The resulting
solution was cooled and titration was continued. Finally the solution was heated to boiling and
titrated further until faint pink color is no longer affected by continued boiling. 1 ml of 1N
hydrochloric acid is equivalent to 0.05299 g of Na2CO3.
• Preparation of 0.5N NaOH: 21 gm of sodium hydroxide pellets were dissolved in sufficient
carbon dioxide free water to produce 1000 ml.
• Standardization of 0.5N NaOH: About 5 g of potassium hydrogen pthalate was weighed
which was previously powdered and dried at 120°C for 2 hours.It was dissolved in 75 ml of
carbon dioxide free water. 0.1 ml of phenolpthalein solution was added and titrated with sodium
hydroxide solution until permanent pink colour was produced. Each ml of 1M sodium
hydroxide is equivalent to 0.2042 g of C8H5KO4.
• The antacid neutralizing capacity of seven liquid and three solid
antacid formulations were estimated using the titration method and pH
meter method.
• Each of tablet containing various ingredients was weighed and then
triturated in mortar and pestle to make a fine powder .The powder was
transferred to a beaker and 70ml of distill water was added and made
to suspension by a magnetic stirrer.
• The liquid antacid bottles were shaken well for one minute and 5ml of
the preparation were poured into a 250ml of glass beaker.70ml of
distill water was added to the antacid formulation in the beaker and
mixed well with a magnetic stirrer for 1 minute.
• Titration method: 30 ml of 1N HCl was pipetted into the prepared drug
solution with continuous stirring. The above preparation was stirred
continuously for about 15 minutes .2-3 drops of methyl orange indicator
was added to the preparation and the excess HCl was titrated with 0.5N
Sodium hydroxide. At the end point the test solution changes from red to
yellow.[14]
•
• pH meter method: 30 ml of 1N HCl was added to the 70ml of the antacid
suspension with constant stirring. The stirring was continued for about
15mins.The excess of the HCl was titrated with 0.5N sodium hydroxide to
attain a stable pH of 3.5
• Both the above procedures were repeated for five times for each sample of
drug and average was taken. [14]
Calculations:
The number of milli equivalents (mEq) of acid consumed was calculated
and the results were expressed in terms of mEq of acid consumed per
gram of substance tested.
Each ml of 1N HCl consumed is equal to 1mEq of acid consumed.
MEq of acid consumed=(V HCl * N HCl) - (V NaOH* NNaOH) where
V HCl =Volume of HCl used in ml
N HCl =Normality of HCl
V NaOH =Volume of NaOH used in ml
N NaOH =Normality of NaOH
List Of Liquid Antacids Formulations And Their Composition Used

Sl/No Sample Al(OH)3mg Mg(OH)2mg Others

1 L1 830 185 Simethicone

2 L2 250 250 Simethicone
3 L3 300 150 Simethicone, Oxethazine

4 L4 125 250 Simethicone, Sodium

alginate

5 L5 600 300 Oxetacaine, Simethicone

6 L6 250 250 Dimethicone, Sodium

alginate

7 L7 500 500 Dimethicone

List of Tablet Antacids Formulations Their Composition

Sl/ Sample Al(OH)3 Mg(OH)2 Others

No mg mg
1 T1 200 400 Alginic acid, Simethicone

2 T2 300 25 Simethicone, Mg Al Silicate

3 T3 250 250
 6. RESULTS AND DISCUSSION
6.1 Results
Acid Neutralizing Capacity of Liquid preparations
Table 1 L1
Sample pH ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.62 21.00 20.75
2 2.59 20.90 20.85
3 2.63 21.05 20.85
4 2.60 20.85 20.70
5 2.61 20.90 20.80
 Table 2 L2
Sample pH ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.42 25.30 25.25
2 2.45 25.35 25.15
3 2.41 25.20 25.05
4 2.48 25.40 25.15
5 2.46 25.35 25.00

Sample Table 3ANCL3pH Meter

pH ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.41 20.20 20.15
2 2.44 20.35 20.20
3 2.40 20.00 20.05
4 2.42 20.10 19.90

5 2.42 20.15 20.20

 Table 4 L4
Sample pH ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.43 21.40 21.25
2 2.42 21.30 21.20
3 2.40 21.50 21.05
4 2.43 21.40 21.25
5 2.44 21.35 21.20

Table 5 L5
Sample pH ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.45 26.65 26.50
2 2.46 26.80 26.60
3 2.45 26.75 26.50
4 2.45 26.75 26.55
5 2.46 26.60 25.50
 Table 6 L6
Sample pH ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.40 25.25 25.50
2 2.42 25.25 24.95
3 2.44 25.35 25.10
4 2.46 25.40 25.05
5 2.50 25.30 24.95

Table 7 L7
Sample pH ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 2.52 25.55 25.50
2 2.50 25.40 25.35
3 2.53 25.60 25.50
4 2.52 25.55 25.60
5 2.50 25.60 25.55
Acid Neutralizing Capacity of Tablet Formulations
Table 8 T1
Sample pH ANC pH Meter ANC
(mEq/Tab.) Titration
(mEq/Tab.)
1 2.63 25.70 25.55
2 2.62 25.75 25.70
3 2.60 25.80 25.70
4 2.61 25.70 26.45
5 2.62 25.85 26.00

Sample pH Table 9 Meter

ANC pH T2 ANC
(mEq/Tab.) Titration
(mEq/Tab.)
1 2.45 23.15 23.05
2 2.43 23.10 23.05
3 2.44 23.20 23.25
4 2.45 23.25 23.00
5 2.42 23.20 23.05
 Table 10 T3
Sample pH ANC pH Meter ANC
(mEq/Tab.) Titration
(mEq/Tab.)
1 2.57 24.00 23.75
2 2.56 23.90 23.90
3 2.58 23.85 23.85
4 2.55 24.10 24.00
5 2.56 24.00 23.90
Table 11 pH meter and titration Acid neutralizing capacity of liquid formulations
Sl/No Sample ANC pH Meter ANC
(mEq/5ml) Titration
(mEq/5ml)
1 L1 20.94 20.79
2 L2 25.32 25.15
3 L3 20.16 20.10
4 L4 21.39 21.19
5 L5 26.71 26.33
6 L6 25.31 25.11
7 L7 25.60 25.55

Table 12 pH meter and Titration

Sl/No Brand ANC of thepHsolid
ANC meter tabletANC
formulations
Titration
mEq/Tab. mEq/Tab.

1 T1 25.76 25.88
2 T2 23.18 23.08
3 T3 23.97 23.88
6.2 Discussion
Antacids are the weak bases used to obtain fast symptomatic relief
from dyspepsia. The potency of the antacids purely depends upon the
acid neutralizing capacity of the individual. In the above study the acid
neutralizing capacity of seven liquid and three solid antacids
formulations were estimated using titration method and pH meter
method. The liquid antacids used were Digene, Alldrox-Gel, Tricaine,
Visco, Digecaine, Gelusil, Normogel. The solid antacids used were Visco,
Digene, Normogel tablets.
Contd…
The liquid formulation L1 had ANC by pH meter 20.94 and titration 20.79, which
had composition of 830mg of aluminium hydroxide and 185mg of magnesium
hydroxide. Similarly L2 had ANC 25.32 and 25.15 by pH meter method and
titration method respectively. The composition of L2 was 250mg of aluminium
hydroxide and 250mg of magnesium hydroxide. The L3 liquid formulation with
composition of aluminium hydroxide 300mg and magnesium hydroxide 150mg
had the ANC pH meter method of 20.16 and titration method 20.10.The ANC of
the liquid formulation L4 by pH meter was 21.39 and by titration method was
21.19. 125mg of aluminium hydroxide and 250mg of magnesium hydroxide was
its composition. Similarly, L5 with a compostion of 600mg aluminium hydroxide
and 300 mg magnesium hydroxide had ANC of 26.71 by pH meter and 26.33 by
titration method.
Contd…
The other two liquid formulations L6 and L7 which had a composition
of aluminium hydroxide 250mg and 500 mg and magnesium hydroxide
250mg and 500mg respectively .Their ANC by pH meter method was
25.31 and 25.60 respectively. Similarly ANC by titration method was
25.11 and 25.55 respectively. From the above results the L5 had the
highest ANC by both pH meter method and titration method. The order
of acid neutralizing capacity of the liquid formulations were L5, L7, L2,
L6, L4, L1 and L3.
Contd…

The solid tablet formulation T1 had ANC 25.76 by pH meter method and
25.88 by titration method. T1 had the combination of 200mg of aluminium
hydroxide and 400mg of magnesium hydroxide. Similarly T2 tablet having
aluminium hydroxide 300mg and magnesium hydroxide 25mg had the ANC
23.18 by pH meter method and 23.08 by titration method. Similarly the ANC
of the T3 tablet by pH meter method was 23.97 and by titration method was
23.88. It had a combination of aluminium hydroxide and magnesium
hydroxide 250 mg and 250mg respectively. Among the solid antacids ANC was
found highest in T1 which had highest magnesium hydroxide concentration.
The order of ANC of solid formulations are T1, T3 and T2 respectively.
Contd…

Acid neutralization capacity of both the tablet and liquid preparation containing
higher amount of magnesium hydroxide was observed to be high as it is a strong,
fast acting antacid which provides faster acid neutralization when compared to
aluminium hydroxide.[20]
As an antacid, magnesium hydroxide suspension neutralizes gastric acid by reacting
with hydrochloric acid in the stomach to form magnesium chloride and water. It is
practically insoluble in water and does not have any effect until it reacts with the
hydrochloric acid in the stomach. There, it decreases the direct acid irritant effect
and increases the pH in the stomach leading to inactivation of pepsin.[21]
 7. CONCLUSION

Neutralizing capacity of various marketed antacids was determined. Acid

neutralizing capacity is the most important factor in determining the potency of the
antacid in providing the symptomatic relief. Acid neutralizing capacity varies
among different antacid and their formulations. It was observed that the formulation
with increased magnesium hydroxide had higher acid neutralizing capacity. The
treating physician can use the antacids with higher neutralizing capacity to obtain
faster symptomatic relief from dyspepsia.
 8. REFERENCE
1. Prakash Katakam, Noha M. Tantosh, Awatef M. Al Eshy, Laila J. Rajab & Abdulbaset A. Elfituri.
A comparative study of the acid neutralizing capacity of various commercially available antacid
formulations in Libya. LIBYAN JOURNAL OF MEDICAL RESEARCH, (2010). 7(1), 42
2. Venkata Vivek G. Comparative study of commercial antacids 2013
3. Abdu, K. and Abbagana, M. Evaluation of Neutralizing Capacity of Different Commercial Brands
of Antacid Tablets. CHEMSEARCH JOURNAL, (2015). 6(2), 32 – 34.
4.https://www.webmd.com/drugs/2/drug-76860-769/antacid-oral/aluminum-magnesium-antacid-
simethicone-oral/details
5. https://www.rxlist.com/antacids/drugs-condition.htm (Date assessed 2018/07/23)
6. Gadhve Manoj V., Garje Vaibhav N., Narad Vaibhav R., Gaikwad D.D & Jadhav S.J. Formulation
development and evaluation of rapidly disintegrating antacid tablets. INTERNATIONAL JOURNAL
OF RECENT SCIENTIFIC RESEARCH, (2016), 7(10), 13802-13806
7. Jensen B.William. Lewis Acid-Base Theory.University of Wisconsin (1974) (40) 11-1
8. James A. Carlson Henry J. Mannand Daniel M. Canafax. Effect of pH on disintegration and
dissolution of ketoconazole tablets. American Journal of Hospital Pharmacy, (1983), 40(8), 1334–
1338.
9. Sharma B. K. Instrumental Methods of Chemical Analysis Twenty Third Edition. Krishna Prakashan
Media.
10. Mary E. MacCara, F. James Nugent & J. Barry Garner. Acid neutralization capacity of Canadian
antacid formulations. CANADIAN MEDICAL ASSOCIATION JOURNAL, (1985). 132(5), 523–527
11. Shery J, Annie S, Shijna A, Reham K & Mariyam I. Acid neutralization capacity and cost
effectiveness of antacids sold across various retail pharmacies in United Arab Emirates. GULF
MEDICAL JOURNAL, (2013), 2(S2), S99-S106
12. http://www.pharmacopeia.cn/v29240/usp29nf24s0_c301.html (accessed 24 th July, 2018)
13. Malviya R., Pant S. and Sharma P.K. Evaluation of acid neutralizing capacity of marketed Digene
tablet. GLOBAL JOURNAL OF PHARMACOLOGY (2015), 9(1), 64-66.
14. K. Jagadesh and Chidananda K. N. Study of acid neutralizing capacity of various antacid
formulations. ASIAN JOURNAL OF PHARMACEUTICAL TECHNOLOGY & INNOVATION, (2015), 03(12),
113 – 120.
15. Tripathi K.D.: Essentials Of Medical Pharmacology, Seventh Edition,Jaypee Brothers Medical
Publishers(P) LTD.
16. United states Pharmacopoeia 24/NF 19, 2000; National Publishing, Philadelphia, PA.
17. Vedavathi H, Tejasvi T S, Shreenivas P. Revankar. Evaluation of cost effectiveness and efficacy
of commonly used different antacid gel preparations. International Journal of Basic & Clinical
Pharmacology (2013), 2(6), 788-791
18. Md. Jakaria, Rashaduz Zaman, Mohammad Parvez, Minhajul Islam, Md. Areeful Haque, Md
Abu Sayeed and Md. Hazrat Ali. Comparative Study among the Different Formulation of Antacid
Tablets by Using Acid-Base Neutralization Reaction. Global Journal of Pharmacology 9 (3): 278-
281, 2015
19. G Chandra Sekhara Rao1, Nalini Kanta Sahoo1, Rabinarayan Parhi and Naresh Panigrah. Study
on the effectiveness of branded and generic antacid suspension forms. Journal of Pharmacy
Research 2011,4(3),612-613
20. https://www.iffgd.org/diet-treatments/antacids.html (Date assessed 2019/03/16)
21. https://www.drugbank.ca/drugs/DB09104 (Date assessed 2019/03/16)