INTRODUCTION:

Endocrine cells, neurons, gastrin, histamine, and acetylcholine all have a role in the regulation of stomach acid output. Throughout history, a number of pharmacological (anti-cholinergic and proton pump) and non-pharmacological (gastric surgery) methods for the inhibition of stomach secretion that can result in ulceration have been presented. The usual treatment for peptic ulcers is antacid therapy, which involves taking medications that increase the pH of stomach acid by either of two mechanisms: directly neutralising acid or preventing acid formation.

Antacids are mostly alkaline chemicals that lower gastric acidity by neutralizing the stomach's hydrochloric acid. Additionally, pharmacological characteristics such as pH range of 3-5, no acid rebound provocation, a rapid beginning of action, sustained efficacy, and strong neutralization potential and capacity have been identified. These are some of the ingredients needed to make modern antacid formulations. By comparing the efficiency of the antacids' preliminary antacid test (PAT), acid neutralizing capacity (ANC), and acid neutralizing potential (ANP), it is possible to compare the variation between antacids Finding an antacid's neutralizing capacity is the best way to express an antacid's capacity to neutralize acid (ANC). ANC gauges an antacid's capacity to neutralize acids (pH of 3.5 to 4).^1,2,3,4

Heartburn, flatulence, dyspepsia, and other symptoms of gastric acidity are frequent conditions that are known to impact a large population of people all over the world.⁵As over-the-counter drugs, antacids are freely accessible in all pharmacies and are a frequently used self-prescribed prescription (OTC). The Food and Drug Administration states that antacids are medications that regulates stomach acidity. They diminish stomach acidity by reducing or inhibiting the release of acid by gastric cells, increasing pH or neutralizing acidity. To lower acidity in the stomach, antacids may increase pH, neutralize acidity, or lower or inhibit the release of acid by gastric cells.⁴ The neutralizing power and stomach transit time of each antacid determine its effectiveness The makers of over-the-counter medicines, such as antacids, frequently redesign some products to goods to enhance their taste and organoleptic characteristics in an effort to draw in customers.^6,7,8

Effervescent Granules:

The dosage form known as granules is composed of dry aggregates of powder particles thatperhaps or notinclude one or more active pharmaceutical ingredient. Citric and tartaric acid are combined to create effervescent granules, which when mixed with water cause CO2 to bubble up. This CO2 functions as a taste masker and excess acid neutralizer. The medication becomes more soluble as a result. Due to their rapid dissolution, high solubility, and stability, effervescent granules are used as common delivery techniques. Before consumption, to begin the effervescence, the dosage form is distributed or dissolved in water.^9,10

Advantages of Effervescent Granules:

1. Simple to administrate.

2. It moves more quickly.

3. Simple to carry on the digestive system.

4. It tastes better.

5. Dose form that is more stable than liquid.

Disadvantages of Effervescent Granules:

1. Cannot be administered to children due to the potential for CO₂ poisoning.

2. There is a danger that external dampness will cause packaging to degrade if it is not done properly.

^3.Its shelf life is less than that of other solid dosage forms.^11,12

Marketed Antacid Powder Sellected for Charectorization

Table1: Marketed Antacid Granules.

Sr. No	Powder name
1	Brand A
2	Brand B
3	Brand C
4	Brand D
5	Brand E

MATERIALS AND METHODS:

Materials:

In order to purchase many brands of antacid granules, a retail pharmacy in Malegaon, Nashik city, Maharashtra, India, was visited. All tests were carried out prior to the products' respective expiration dates. 0.5 N HCl, 1N HCl, 0.5 N NaOH and 0.1 N HCl were the reagents that were utilised inthis experiment. All the ingredients used for this work are of the analytical grade. Distilled water was used during the entire procedure.

Instrumentation:

HANNA instruments’ pHep^R pocket sized pH meter is an instrument of choice for detection of pH. REMI MS 500 Magnetic stirrer manufactured by REMI ELEKTROTECHNIK LIMITED is an equipment used for stirring or mixing a solution.

Characterization of marketed antacid granules:

Characterization of marketed antacid granules was carried out by using following ways.

Angle of Repose:

The angle that distinguishes the transitions between the granular material's phases is known as the angle of repose.¹³The angle of repose must be taken into account when designing systems for processing, storing, and transporting particulate material. It is crucial for the investigation of a drug's flow properties. The angle of repose is small when the granules are spherical and smooth. The angle of repose is high for granules that are extremely fine and sticky. Low angle of repose granules are very flowable. A funnel with a 10 mm stem diameter was suspended over the platform at a height of 2 cm. A 10 g sample was gently moved along the funnel's wall until the pile's tip developed and made contact with the funnel's stem. After drawing a broad arc around the pile's base, the radius of the powder cone was determined.¹⁴Angle of repose is determined by following formula:

Angle of Repose = tan^-1(h/r).

Where,

H = height

R = radius

Bulk Density:

Bulk density is a characteristic that can be utilized to check the homogeneity of the large granules, choose the the right-sized containerand equipment for blending in manufacturing, and establish the right size for the packaging granules.¹⁵ It was performed in a way that a mixture of 15g of carefully measured granules was placed in a graduated cylinder with a capacity of 50 ml. Without compacting the granules, the surface was carefully levelled, and the actual volume of bulk was calculated.¹⁶Bulk density is calculated using the given formula:

Bulk density = Wt of Granule in gm/Bulk volume

Tapped Density:

The tapped density is assessed primarily for two reason. That are it can be measured more consistently than the bulk densityand the ratio between these two measured densities can be used to determine a powder's "flowability."¹⁷In order to complete the procedure, 15 g of granules were precisely transferred into a graduated cylinder with a 50 ml capacity. Then, after being raised and let to fall to the ground naturally, the cylinder was mechanically tapped. The cylinder had 500 taps made on it.^18,19

The formula below is used to calculate it:

Tapped density = wt of Granule/Tapped volume.

Carr’s index:

For a solid's ability to be compressed into a powder, theCarr’sIndex is computed applying the true density (ρT) and bulk density (ρB). When the Carr index is larger than 25, flowability is considered to be poor, and when it is lower than 15, flowability is considered to be good.^20,21Carr's Index's formula is as follows:

Carr’s index (%) = TD-BD*100/Bulk density

Where, TD = Tapped Density

BD = Bulk Density

Hausner’s ratio:

The flowability of a powder or granular substance is connected with a value called the Hausner ratio.²²

Formula for Hausner’s ratio:

Hausner’s ratio = TD/BD.

Where, TD = Tapped Density

BD = Bulk Density

Effervescence Time:

When a clear solution is created, the effervescent time of the granules will be recorded. To measure this, one dose of granules was added to a glass containing 250 ml of water.²³

Preliminaery Antacid Test (PAT):

The test was carried out to determine whether the mixture meets the antacid’s definition, where pH greater than 3.5 is required for the antacid-acid (HCl) solution.²⁴The smallest recommended amount of 5 grammes of material was carefully weighed and then poured into a 100 ml beaker. The mixture was thoroughly swirled on a magnetic stirrer for a minute at 300±30rpm after adding the appropriate amount of water. Then 10ml of 0.5N HCl was added, and the test solution was then stirred for approximately 10minutes on the magnetic stirrer. The pH of the combination was observed. The sample ought to reach a pH of greater than 3.5 in just 10 minutes. The antacid label may be applied to the samples that pass this test.^25,26,27

Acid Neutralizing Test (ANC):

This testserves to determine whether an antacid composition is effective.²⁸ For a formulation to qualify as an antacid, the ANC value per dosage (minimum labeled dose) must be more than 5mg. Test solution was prepared by transferring a precisely weighed quantity of the material to a 250ml beaker. The mixture was magnetically mixed for 1minute after receiving a total of about 70ml of water. The test solution made using the aforementioned procedure was pipetted with 30 ml of 1N HCl, and the mixture was then kept for magnetic stirrer stirring. The mixture was accurately agitated 5 minutes after the acid was added, and was then quickly and within the next 5 minutes, at most, titrated. 0.5 N NaOH was used to titrate more HCl in order to keep the pH at 3.5. The acid neutralising capacity was calculated as the amount of acid that would be required to neutralise one mEq of 1N HCl in one millilitre. The solution temperature was maintained at 370±10C during the entire experiment. The outcomes were presented asthe acid’s amount consumed per dosage of the test chemical, expressed in terms of mEq of acid.^29,30,31,32

Reheis Test:

It measures the speed at which the medicine neutralises the acid by measuring the amount of time it takes to bring pH to 3.0.³³

Rosette-Rice Test:

The amount of time that the antacid medications maintained the pH of a simulated stomach solution at 3.0 to 5.0 was measured using a modified Rossett-Rice test.³⁴It's a dynamic acid-neutralizing test. The efficacy of an antacid dosage is assessed using an in vitro method. The pH profile of the stomach's neutralising acid was measured while the stomach was stimulated in the Rosette-Rice test. An amount of pure water and 70 ml of 0.1 N HCl were added to a 500ml reaction beaker in accordance with the pH profile during the neutralisation procedure. An equivalent weight of tablet sample was introduced while the magnetic stirring was occurring at 37°C and put it in the reaction vessel. Then, from a burette, 0.1N hydrochloric acid was administered continuouslyat a rate of 2ml/min. Using a pH metre, the pH of the reacting vessel was tracked during the neutralization procedure. Both the duration needed to achieve pH 3.0 and the Rosette-Rice time (RRT), which is the time period needed to keep the pH levels between 3.0 and 5.0, were recorded. Additionally, the pH variations were seen with relation to time.³⁵

RESULT AND DISCUSSION:

Result of General Appearance:

Brand A, Brand B, Brand C, Brand D, and Brand E are of Yellowish green, Pink, Light yellow, Light blue and Yellowish green colour respectively. Brand A, Brand C, Brand D and Brand E are of Lemon flavor while Brand B is of Guava flavor. Each of the five brands has sour test.

Table 2: General Appearance.

Sr. No	Brand	Colour	Flavor	Taste
1	Brand A	Yellowish- Green	Lemon	Sour
2	Brand B	Pink	Guava	Sour
3	Brand C	Light- Yellow	Lemon	Sour
4	Brand D	Light blue	Lemon	Sour
5	Brand E	Yellowish- Green	Lemon	Sour

Result Evaluation of Granules:

According to values of angle of repose, each of all antacid brands had fair flow. Percentage of Carr's index indicated that Brands A, B, and D had good flow properties, Brand C had fair flow properties, and Brand E had passable flow property. According to Hausner’s ratio, Brands A, B, C and D had Good flow property while Brand E had fair flow property.

Table 3: Evaluation of Powder.

Sr. No	Brand	Bulkdensity(g/mL)	Tappeddensity (g/mL)	Angle of repose (ф)	% Carr’s index (CCI)	Hausner’s ratio
1	Brand A	0.90	1.0345	35.37	14.94	1.14
2	Brand B	0.93	1.07	35.37	15.05	1.15
3	Brand C	0.89	1.05	36.50	17.97	1.17
4	Brand D	0.90	1.01	35.52	12.22	1.12
5	Brand E	0.90	1.11	37.59	23.33	1.23

Effervescent Time:

Brand Ahad less effervescent time as compared to other brands and Brand Dhad higher effervescent time as compared to other brands.

Table 4: Effervecent Time.

Sr. No	Brand	Effervescent time
1	Brand A	50 sec
2	Brand B	1 min 2 sec
3	Brand C	55 sec
4	Brand D	1 min 9 sec
5	Brand E	1min 3 sec

Preliminary Antacid Test (PAT):

Since the antacid-acid (HCl) solution’s pH for each brand was found to be higher than pH 3.5, all of the brands were considered as antacids.

Table 5: Preliminary Antacid Test.

Sr. No	Brand	pH of mixture (after 10min)
1	Brand A	5.8
2	Brand B	5
3	Brand C	5.6
4	Brand D	5.8
5	Brand E	5.7

Acid Neutralizing Capacity Test (ANC)

The capacity of acid neutralization as revealed by the following table indicated that all brands of antacids do not meet the US FDA requirement that an antacids must have acid neutralization capacity of >5 mEq per dose.

Table 6: Acid Neutralizing Capacity Test.

Sr. No	Brand	ANC
1	Brand A	27.75
2	Brand B	27.05
3	Brand C	26.6
4	Brand D	27.45
5	Brand E	26.45

Reheis Test:

As per Reheis test Brand D required less time for neutralization as compared to other brands and Brand B required more time for neutralization as compared to other brands.

Table 7: Reheis Test

Sr. No	Brand	Reheis time
1	Brand A	2 min 10 sec
2	Brand B	4 min 25 sec
3	Brand C	3 min 29 sec
4	Brand D	1 min 05 sec
5	Brand E	4 min

Rosette-Rice Test:

As per Rosette rice test Brand A required less time to maintain the pH between 3 to 5 and Brand D requiredmore time for the same.

Table 8: Rosette-Rice Time Profile of Formulation.

Sr. no	Time (in min)	pH of mixture of formulation
Sr. no	Time (in min)	Brand A	Brand B	Brand C	Brand D	Brand E
1	0	5.6	4.5	5.1	5.3	5.2
2	5	5.2	4.2	4.8	4.9	4.9
3	10	4.8	3.8	4.4	4.5	4.5
4	15	4.5	3.3	3.9	3.9	3.9
5	20	3.9	3.0	3.2	3.4	3.4
6	25	3.3	2.8	2.9	3.5	3.1
7	30	3.0	2.4	2.4	3.0	2.8

Table 9: Rosette-Rice Time.

Sr. No	Brand	Rosette rice test in min
1	Brand A	20 min 00sec
2	Brand B	25min 18 sec
3	Brand C	21 min 09 sec
4	Brand D	26 min 34 sec
5	Brand E	25 min 45 sec

Figure 1: Rosette-Rice Time Profile

CONCLUSION:

The values of bulk density, tapped density, angle of repose, carr's index, and hausner's ratio during the evaluation of various antacid granules in the market show that Brands A, B, and D have good flow property, Brand C has fair property, and Brand E has passable flow property.Brand D has a longer effervescent time than other brands, while Brand A has a shorter effervescent duration than other brands.All of the brands are regarded as antacids because the pH of the antacid-acid (HCl) solution for each brand is discovered to be higher than pH 3.5.All antacid products fail to meet the US FDA requirement that they have an acid neutralizing capacity of at least 5 mEq, according to the acid neutralizing capacity (ANC) test. According to the Reheis test, Brand D required less time for neutralization than other brands, but Brand B required more time than other brands. According to the Rosette rice test, Brand A needed less time than other brands to keep the pH level between 3 and 5, whereas Brand D needed more time.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENT:

Authors express their sincere gratitude to SSS’s Divine College ofPharmacy, Satana, Nashik for continuous motivation, support, and guidance for such activity andfor providing all required facilities to accomplish the entitled work.

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Received on 20.01.2023 Modified on 10.04.2023

Asian J. Res. Pharm. Sci. 2023; 13(3):201-205.

DOI: 10.52711/2231-5659.2023.00035