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DETERMINATION OF ACID NEUTRALIZING CAPACITY OF VARIOUS

MARKETED ANTACIDS IN NEPAL

BY

SHIVA ARYAL

A DISSERTATION SUBMITTED TO THE

TRIBHUVAN UNIVERSITY

IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR


THE DEGREE OF

BACHELOR OF PHARMACY

DEPARTMENT OF PHARMACY

NATIONAL MODEL COLLEGE FOR ADVANCE LEARNING

KHUSIBU, KATHMANDU

FEBRUARY 2019

NATIONAL MODEL COLLEGE FOR ADVANCE LEARNING

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CERTIFICATION

This is to certify that the dissertation entitled " DETERMINATION OF ACID


NEUTRALIZING CAPACITY OF VARIOUS MARKETED ANTACIDS IN
NEPAL"is a bonafide research work done by "SHIVA ARYAL" in partial
fulfillment of the requirement for the degree of Bachelor in Pharmacy. This
research work was carried out under our guidance and supervision.

.........................................

Mr. Anil Prasad Shah

(Supervisor)

Lecturer

Department Of Pharmacy

NMCAL

………………………….

External Examiner

NATIONAL MODEL COLLEGE FOR


ADVANCE LEARNING

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ENDORSEMENT BY THE PRINCIPAL/HOD

This is to certify that the dissertation entitled " DETERMINATION OF ACID


NEUTRALIZING CAPACITY OF VARIOUS MARKETED ANTACIDS IN
NEPAL " is a bonafide research work done by "Shiva Aryal" at National Model
College for Advance Learning (NMCAL).

Approved by:

.............................................

----------------------

Head of Department

NMCAL

ACKNOWLEDGEMENTS

The first and foremost gratitude goes to Dr. Madhav Prasad Baral, Chairperson and Mr. Prajwal
Jung Pandey, Head of Department, National Model College for Advance Learning for their
support during the course of this study.

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I am also pleased to express my deep gratitude and respect to my thesis supervisors Mr. Anil
Prasad Shah, lecturers of National Model College for Advance Learning, Tribhuvan University
for their valuable and continuous guidance, encouragement, supervision and timely suggestions
in all stages of thesis without which this project wouldn't have been productively accomplished.

I would also like to express my sincere appreciation to Ms. Sabyata Gautam, co-ordinator of
National Model College for Advance Learning, for their valuable suggestions regarding
formulation processing.

An equal gratitude and appreciation goes to Mr. Suresh Rai for his tremendous support and help,
in creating a proper working environment in the laboratory.

Finally, I would like to convey my heartfelt thanks to all my friends and family members for
their suggestions, well-wishers and moral support and all the people who provided me guidance
and assistance during this dissertation work.

Shiva Aryal

Abstract

Antacids are the substances most commonly used by the patients to obtain fast symptomatic
relief from dyspepsia. They are the week base which neutralize the gastric acid and raise the pH
of the gastric contents. The potency of the antacids depends upon their acid neutralizing capacity
(ANC). The antacid neutralizing capacity varies from one another depending upon their

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formulations. The present study was undertaken to study the acid neutralizing capacity of
commonly available antacids formulations using titration and pH meter method. Seven liquid
formulations and three solid tablet formulations were studied for their acid neutralizing capacity.
The acid neutralizing capacity among the liquid formulations was highest for Digecaine 26.71 by
pH meter method and 26 by titration method. Among solid antacid formulations ANC was
highest with Visco being 25.76 by pH meter method and 25.88 by titration method. Both the
formulations had higher magnesium hydroxide concentration when compared to other antacids.
The acid neutralizing capacity was highest with the antacids containing magnesium hydroxide.
For acute fast symptomatic relief from dyspepsia antacids containing higher concentration of
magnesium hydroxide would be helpful.

Abbreviation

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Contents

1. INTRODUCTION.................................................................................................................6

1.1 Working of Antacids............................................................................................................7

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1.2 Types of Antacids.................................................................................................................8

1.3 Side effects............................................................................................................................9

1.4 Problems related with reduced stomach acidity.............................................................10

1.5 Explanation of action of neutralization of antacids..........................................................2

1.6 Determination of concentrations of substances in neutralization...................................2

1.7 Literature Review................................................................................................................3

1.8 Rationality of study..............................................................................................................4

2. MATERIALS AND METHODS...............................................................................................4

2.1 Materials required...............................................................................................................4

2.2 Equipments and Instruments Required............................................................................5

2.3 Methodology....................................................................................................................5

3. RESULTS AND DISCUSSION.................................................................................................7

List of figure

Figure 1 Working of antacids.......................................................................................................7

Table 1 List Of liquid Antacids Formulations And Their Composition Used.........................6


Table 2 List of Tablet antacids and their composition................................................................6
Table 3 Digene Gel.........................................................................................................................7
Table 4 Alldrox-Gel........................................................................................................................7
Table 5 Tricaine..............................................................................................................................7
Table 6 Visco Syrup.......................................................................................................................8
Table 7 Digecaine...........................................................................................................................8
Table 8 Gelusil................................................................................................................................9
Table 9 Normogel Suspension.......................................................................................................9

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Table 10 Visco Tablet.....................................................................................................................9
Table 11 Digene Tablet.................................................................................................................10
Table 12 Normogel Tablet...........................................................................................................10
Table 13 pH meter and titration Acid neutralizing capacity of liquid formulations.............10
Table 14 : pH meter and Titration ANC of the solid tablet formulations...............................11

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1. INTRODUCTION
It is well known that the food we take undergoes a series of complex reactions within the body
which constitute digestion and metabolism. These reactions are catalyzed by enzymes which are
very specific in their action and can function properly only when the pH of the medium is within
a specific range.

Some enzymes require mildly alkaline conditions while others operate only in weakly acidic
media. Amongst the latter category of enzymes are the enzymes that control the digestion of
proteins present in the food as it reaches the stomach. In the stomach, dilute hydrochloric acid is
secreted and it provides mildly acidic conditions required for the functioning of protein digesting
enzymes in the stomach.

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). It is produced by cells lining the stomach, which are coupled
to systems to increase acid production when needed.

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. The bicarbonate-secreting cells in the stomach also produce
and secrete mucus. Mucus forms a viscous physical barrier to prevent gastric acid from
damaging the stomach.

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 to much
food or highly spiced food. This, in turn, makes the stomach lining cells to secrete more acid
resulting in Hyperacidity. It also leads to acute discomfort due to indigestion.

To counter this situation, substances like Antacids or literally anti - acids, 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.
Common antacids satisfy the condition – right amount of alkali that can neutralize the acid. If the
content of alkali in the antacid is too high, no doubt acidity is relieved, but it’ll create alkaline
conditions that makes the digestive enzymes ineffective.

To make sure that the pH of the stomach remains in a specific range, many substances are added
to the antacids.

1.1 Working of Antacids

Figure 1 Working of antacids

If the antacid contains NaHCO 3 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.

1.2 Types of Antacids

 Sodium Antacids (Alka-Seltzer, Bromo-Seltzer and Others): 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.

 Calcium Antacids (Tums, Alka-2, Titralac and Others): Antacids in the form of calcium
carbonate or 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. Extended use of calcium antacids can also cause kidney stones.

 Magnesium Antacids (Maalox, Mylanta, Riopan, Gelusil and Others): Magnesium salts
come in many forms -- carbonate, glycinate, hydroxide, oxide, trisilicate, and
aluminosilicate. Magnesium has a mild laxative effect; it can cause diarrhea. For this
reason, magnesium salts are rarely used as the only active ingredients in an antacid, but
are combined with aluminum, which counteracts the laxative effect. (The brand names
listed above all contain magnesium-aluminum combinations.) Like calcium, magnesium
may cause kidney stones if taken for a prolonged period, especially if the kidneys are
functioning improperly to begin with. A serious magnesium overload in the bloodstream
(hypermagnesaemia) can also cause blood pressure to drop, leading to respiratory or
cardiac depression -- a potentially dangerous decrease in lung or heart function.

Aluminum Antacids (Rolaids, ALternaGEL, Amphojel and Others): Salts of aluminum


(hydroxide, carbonate gel, or phosphate gel) can also cause constipation. For these reasons,
aluminum is usually used in combination with the other three primary ingredients. Used heavily
over an extended period, antacids containing aluminum can weaken bones, especially in people
who have kidney problems. Aluminum can cause dietary phosphates, calcium, and fluoride to
leave the body, eventually causing bone problems such as osteomalacia or osteoporosis.

1.3 Side effects


 Calcium: Excess calcium from supplements, fortified food and high-calcium diets, can
cause milk-alkali syndrome, which has serious toxicity and can be fatal.

 Carbonate: Regular high doses may cause alkalosis, which in turn may result in altered
excretion of other drugs, and kidney stones. A chemical reaction between the carbonate
and hydrochloric acid may produce carbon dioxide gas. This causes gastric distension
which may not be well tolerated. Carbon dioxide formation can also lead to headaches
and decreased muscle flexibility.

 Aluminum hydroxide: May lead to the formation of insoluble aluminium-phosphate-


complexes, with a risk for hypophosphatemia and osteomalacia. Although aluminium has
a low gastrointestinal absorption, accumulation may occur mainly in the presence of renal
insufficiency. Aluminium-containing drugs often cause constipation and are neurotoxic.

 Magnesium hydroxide: Has laxative properties. Magnesium may accumulate in patients


with renal failure leading to hypermagnesaemia, with cardiovascular and neurological
complications.

 Sodium: increased intake of sodium may be deleterious for arterial hypertension, heart
failure and many renal diseases.

 Heartburn, reflux, indigestion, and sour stomach are a few of the common terms used to
describe digestive upset. Self-diagnosis of indigestion does carry some risk because the
causes can vary from a minor dietary indiscretion to a peptic ulcer
 The pain and symptoms of GERD or simply "reflux", may mimic those of a heart attack.
Misdiagnosis can be fatal. A bleeding ulcer can be life threatening.

 GERD and pre-ulcerative conditions in the stomach are treated much more aggressively
since both, if untreated, could lead to esophageal or stomach cancer.

 It is primarily for this reason that the H2 blockers including cimetidine (Tagamet),
famotidine (Pepcid), and ranitidine (Zantac), and the proton pump inhibitor (PPI)
omeprazole (Prilosec) were made OTC.

 These drugs stop production of stomach acid and provide longer lasting relief but they do
not neutralize any stomach acid already present in the stomach.

1.4 Problems related with reduced stomach acidity


 Reduced stomach acidity may result in an impaired ability to digest and absorb certain
nutrients, such as iron and the B vitamins. Since the low pH of the stomach normally kills
ingested bacteria, antacids increase the vulnerability to infection. It could also result in
the reduced bioavailability of some drugs. For example, the bioavailability of
ketocanazole (anti-fungal) is reduced at high intragastric pH (low acid content).

Over usage of antacids naturally have side-effects. As with anything in life, it must be used in
moderation. The following flowchart elucidates very clearly.
Figure 2 Problems with reduced stomach acidity

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1.5 Explanation of action of neutralization of antacids
The Lewis definition of acid-base reactions is a donation mechanism, which
conversely attributes the donation of electron pairs from bases and the acceptance by
acids.
+
Ag + 2 :NH3 → [H3N :Ag: NH3]+
(A silver cation reacts as an acid with ammonia which acts as an electron-pair donor, forming an
ammonia-silver adduct)
In reactions between Lewis acids and bases, there is the formation of an adduct when the highest
occupied molecular orbital (HOMO) of a molecule, such as NH 3 with available lone electron
pair(s) donates lone pairs of electrons to the electron-deficient molecule's lowest unoccupied
molecular orbital (LUMO) through a co-ordinate covalent bond; in such a reaction, the HOMO-
interacting molecule acts as a base, and the LUMO-interacting molecule acts as an acid. In
highly-polar molecules, such as boron trifluoride (BF 3), the most electronegative element pulls
electrons towards its own orbitals, providing a more positive charge on the less-electronegative
element and a difference in its electronic structure due to the axial or equatorial orbiting positions
of its electrons, causing repulsive effects from lone pair-bonding pair (Lp-Bp) interactions
between bonded atoms in excess of those already provided by bonding pair-bonding pair (Bp-
Bp) interactions.
X

1.6 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. It makes use of the neutralization reaction that occurs between acids and bases, and that
we know how acids and bases will react if we know their formula.
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,
will have a pH dependent on the relative strengths of the acid and base used.
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. At this point the solution is very slightly basic, with a negligible amount of
excess NaOH. 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. Several antacids will be tested and the relative strengths of each will
be compared.

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1.7 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.

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.

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1.8 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 10 years have witnessed many changes in
antacid formulations. 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, 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 both the rate and 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 of formulations.

1. To determine the acid neutralizing capacity of various marketed antacids.

2. To help pharmacists and practicing physicians to choose the best drug among a very large
number of formulations.

2. MATERIALS AND METHODS

2.1 Materials required


I. Sample

 Marketed Antacids (2 batches each)

II. Chemicals

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 1N HCL
 0.5N NaOH
 Methyl orange
 Phenopthalein

2.2 Equipments and Instruments Required

 Electronic Balance, d=0.0001 g, Max=110g, model: Adventurer Pro AU114


(Ohaus Corporation Pine Brook, NJUSA)

 Beaker

 Burette

 Conical flask

 pH meter, model: CL180 (Labline Technology)

 Magnetic Stirrer

 Filter paper (Whatman)

2.3 Methodology
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

5
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.

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.

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

Table 1 List Of liquid Antacids Formulations And Their Composition Used

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


1 Digene 830 185 Simethicone
2 Alldrox-Gel 250 250 Simethicone
3 Tricaine 300 150 Simethicone, Oxethazine
4 Visco 125 250 Simethicone, Sodium alginate
5 Digecaine 600 300 Oxetacaine, Simethicone
6 Gelusil 250 250 Dimethicone, Sodium
alginate
7 Normogel 500 500 Dimethicone

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Table 2 List of Tablet antacids and their composition

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


1 Visco 200 400 Alginic acid, Simethicone
2 Digene 300 25 Simethicone, Mg Al Silicate
3 Normogel 250 250

3. RESULTS AND DISCUSSION

3.1 Results: Liquid preparations

Table 3 Digene Gel

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
Mean ±SD ANC pH meter=20.94, ANC Titration=20.79

Table 4 Alldrox-Gel

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
Mean ±SD ANC pH meter=25.32, ANC Titration=25.12

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Table 5 Tricaine

Sample pH ANC pH Meter 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
Mean ±SD ANC pH meter=20.16, ANC Titration=20.10

Table 6 Visco Syrup

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
Mean ±SD ANC pH meter=21.39, ANC Titration=21.19

Table 7 Digecaine

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
Mean ±SD ANC pH meter=26.71, ANC Titration=26.33

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Table 8 Gelusil

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
Mean ±SD ANC pH meter=25.31, ANC Titration=25.11

Table 9 Normogel Suspension

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
Mean ±SD ANC pH meter=25.54, ANC Titration=25.50

Tablet Formulations

Table 10 Visco Tablet

Sample pH ANC pH Meter ANC


(mEq/5ml) Titration (mEq/5ml)
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
Mean ±SD ANC pH meter=25.76, ANC Titration=25.88

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Table 11 Digene Tablet

Sample pH ANC pH Meter ANC


(mEq/5ml) Titration (mEq/5ml)
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
Mean ±SD ANC pH meter=23.18, ANC Titration=23.08

Table 12 Normogel Tablet

Sample pH ANC pH Meter ANC


(mEq/5ml) Titration (mEq/5ml)
1 2.57 24.00 23.75
2 2.56 23.90 23.90
3 2.58 23.83 23.85
4 2.55 24.10 24.00
5 2.56 24.00 23.90
Mean ±SD ANC pH meter=23.96, ANC Titration=23.88

Table 13 pH meter and titration Acid neutralizing capacity of liquid


formulations

Sl/No Brand ANC pH Meter ANC


(mEq/5ml) Titration (mEq/5ml)
1 Digene 20.94 20.79
2 Alldrox-Gel 25.32 25.15
3 Tricaine 20.16 20.10
4 Visco 21.39 21.19
5 Digecaine 26.71 26.33
6 Gelusil 25.31 25.11
7 Normogel 25.60 25.55

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Table 14 : pH meter and Titration ANC of the solid tablet formulations

Sl/No Brand ANC pH meter ANC Titration


mEq/gm mEq/gm
1 Visco 25.76 25.88
2 Digene 23.18 23.08
3 Normogel 23.96 23.88

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