Acid-neutralising capacity and pharmacoeconomic studies of commercially available antacids in the Qassim Region of Saudi Arabia

Danish Mahmood; Sulaiman Alnaseer; Bala Yauri Muhammad; Habibullah Khalilullah; Mahfoudh A M Abdulghani; Md Jamir Anwar; Sattam K Alenezi; Mohammad Haider; Nasra Elleban

doi:10.4103/HMJ.HMJ_10_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 13 | Issue : 3 | Page : 150-155

Acid-neutralising capacity and pharmacoeconomic studies of commercially available antacids in the Qassim Region of Saudi Arabia

Danish Mahmood¹, Sulaiman Alnaseer¹, Bala Yauri Muhammad¹, Habibullah Khalilullah², Mahfoudh A M Abdulghani¹, Md Jamir Anwar¹, Sattam K Alenezi¹, Mohammad Haider¹, Nasra Elleban¹
¹ Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Unaizah, Qassim University, Qassim, Saudi Arabia
² Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Unaizah, Qassim University, Qassim, Saudi Arabia

Date of Submission	27-Jan-2020
Date of Decision	07-Apr-2020
Date of Acceptance	16-Mar-2020
Date of Web Publication	2-Sep-2020

Correspondence Address:
Danish Mahmood
Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Al Qassim
Saudi Arabia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/HMJ.HMJ_10_20

Abstract

Background: Antacids are common over-the-counter medications for relief in common dyspeptic symptoms. However, antacid use has decreased with the availability powerful acid suppressant medications such as histamine H2 blockers, proton-pump inhibitors and prostaglandin analogues. Of late, a resurgence in the usage of antacids has been noted because of the improved profiles of newer antacid formulations, for example, the addition of pain-relieving component, oxetacaine (a local anaesthetic), anti-flatulent (alginate base compounds), in some antacid preparations. Aims and Objectives: The study investigated the efficacy (in terms of acid-neutralising capacity [ANC]) and cost-effectiveness of commercially available antacid formulations (both liquid and solid formulations). Materials and Methods: ANC was carried out using simple titrimetric methods and cost-effectiveness of antacid preparations was based on cost (in Saudi riyal) per milliequivalents of the acid neutralised. Results: ANC/gram was highest for antacid A1 (Moxal Plus solid) and lowest for antacid A3 (Fawar effervescent powder). The ANC/gram varied greatly among different antacid products and it ranged from 3.48 to 13.18. In general, solid antacids showed a high ANC/gram compared to the liquid antacids. Furthermore, solid antacids were also found to be cost-effective compared to liquid dosage forms. In terms of efficacy, the newer antacid containing simethicone (A1) was found to be more cost-effective followed an antacid containing calcium carbonate (A2) and magnesium carbonate. Conclusion: In conclusion, mentioning ANC on antacid formulation labels may help to guide the choice of appropriate antacid, while cost-effectiveness study would govern the prescribing pattern of an antacid.

Keywords: Antacid, dyspepsia, H₂blockers, proton-pump inhibitors, simethicone

How to cite this article:
Mahmood D, Alnaseer S, Muhammad BY, Khalilullah H, M Abdulghani MA, Anwar MJ, Alenezi SK, Haider M, Elleban N. Acid-neutralising capacity and pharmacoeconomic studies of commercially available antacids in the Qassim Region of Saudi Arabia. Hamdan Med J 2020;13:150-5

How to cite this URL:
Mahmood D, Alnaseer S, Muhammad BY, Khalilullah H, M Abdulghani MA, Anwar MJ, Alenezi SK, Haider M, Elleban N. Acid-neutralising capacity and pharmacoeconomic studies of commercially available antacids in the Qassim Region of Saudi Arabia. Hamdan Med J [serial online] 2020 [cited 2023 Mar 29];13:150-5. Available from: http://www.hamdanjournal.org/text.asp?2020/13/3/150/294171

Introduction

Antacids are common over-the-counter requiring no physicians' prescription, used for relief in common dyspeptic symptoms. These medications are very good at providing initial symptom relief in gastroesophageal reflux disorder (GERD), gastritis, peptic ulcer and duodenal ulcer.

Gastric-related diseases represent considerable burden to the health-care services, with appreciable number of people suffering from these disorders each year which constitute half of the gastroenterology referrals with these symptoms.^[1] Of late, increasing cases of gastric-related problems have been reported which were not so common in Saudi Arabia. In 2017, a study involving people of Arar City of the Kingdom recorded substantially high presence of GERD (61.8%), gastric ulcer (16.2%) and duodenal ulcers (5.6%).^[2],[3] Another recent study, also, reported consistent finding among citizens of Saudi Arabia and the number of such cases was even higher than those in Western and East Asian countries.^[4]

The availability of newer and more efficacious acid suppressant (anti-secretory) medications has lowered the use of antacids. However, a resurgence of the use of antacids has been noted in recent years, possibly because of some serious undesirable effects attributed to the prolonged use of medications such as H₂ blockers and proton-pump inhibitors. H₂ blockers, used for a long time, are frequently associated with postprandial acid control and tachyphylaxis,^[5] and recently, alteration in intestinal flora and impairment of nutrients absorption, increase risk of cardiovascular problems, renal diseases, and among others memory loss have been reported with the use of proton-pump inhibitors.^{[6],[7],[8],[9]} Hence, antacids are relatively safe and cost-effective in comparison to H₂ blockers and proton-pump inhibitors.^{[10],[11],[12]}

Acid-neutralising capacity (ANC) refers to the ability of an antacid to neutralise gastric acid at a temperature of 37°C ± 2°C and it is denoted in milli-equivalents (mEqs). Antacids work by neutralising hydrochloric acid (HCl) released from the gastric cells and thereby increase the gastric pH. When the stomach pH is elevated to pH >3, the excess HCl released is mostly neutralised and proteolytic activity of pepsin is suppressed. Thus, antacid works through several mechanisms which include direct neutralisation of acids, pH elevation or reversibly inhibiting or suppressing the gastric acid release.^[13] Aside from these mechanisms, antacids lower peptic activity by acting on pepsins. It has been reported that the efficacy of antacid not only depends on its ability to neutralise acids but also on the time taken by antacid to reach the stomach, i.e., its transit time. Antacids are present in different forms, namely tablet, powder, liquid, suspensions and gel formulations. Liquid antacids are more efficacious compared to their solid (tablets) counterparts because they are already in their dissolved form,^[14] and gel-based antacids have advantage over other forms of antacid because they provide a protective coat over the inflamed mucous membrane.^[15]

The composition of antacid preparations frequently includes sodium bicarbonate (NaHCO₃), calcium carbonate (CaCO₃), aluminium hydroxide/phosphate (Al (OH)₃/AlPO₄) and magnesium citrate/carbonate/oxide/hydroxide (Mg-citrate/magnesium carbonate [MgCO₃]/MgO/Mg[OH]₂).^[16] Magnesium salts act fast and salts of aluminium act slowly, hence, both are combined to provide a long-lasting acid neutralisation effect. Therefore, to provide a balanced action, laxative effect of magnesium is taken care of by the constipating effect of aluminium salts.^[17]

Any good antacid is expected to have maximum ANC and it should provide the greatest amount of acid neutralization per unit cost. A low-priced antacid having long-lasting effect, pleasant in taste and ease of consumption is most often preferred. Furthermore, antacids which are not absorbed systemically or cause alkalosis or rebound hyperacidity, and those that do not hamper processes such as absorption and digestion because they are insoluble basic com¬pound and can be used either alone or in combination.^[18],[19]

Recently, newer antacid formulations have been introduced which claim to have a better efficacy in terms of ANC. One of the antacid formulations included oxetacaine (oxethazaine), a local anaesthetic component, which offers fast and long-lasting relief from gastric pain of peptic ulcer disease or oesophagitis. Another formulation contains simethicone/dimethicone, an antifoaming agent, which has been reported to prevent gas formation in the digestive tract of patients who have chronic problem of flatulence. Yet, another antacid formulation combines alginate, a natural polymer, which precipitates into a viscous gel of neutral pH, after interaction with gastric acid. The precipitation takes place within few seconds (in vitro) or a few minutes (in vivo). These antacids form a protective coat and also increase viscosity and adherence of mucus to the oesophageal mucosa.^[20] These newer antacid formulations claim better potency compared to traditional antacid formulation, making them expensive, but the efficacy of antacid should be judged by its ANC, and therefore, the cost of antacid should be based on its capacity to neutralise acid and not the additional component in it which plays no or little role in ANC of an antacid.^[21]

As antacids are the third most commonly sold over-the-counter medications after analgesic and anti-allergic drugs.^[22] It is warranted that these medications' sale should be guided by studies providing data on their pharmacoeconomic profiles, most importantly the cost per strip/vials of particular antacids, and comparative analytical data for their efficacy before being recommended by a clinician, and also, it may prevent antacid misuse. As there is an abundance of antacids available in the market and many more will enter into the market for sale, and hence, from both patient and clinician's perspective, it is imperative to study the cost-effectiveness and efficacy of various antacid formulation available in the local market.^[23] Therefore, this research project is designed to investigate ANC and the cost-effectiveness of some commercially available antacid brands in the Qassim region of the Saudi Arabia.

Materials and Methods

Drugs and chemicals

The commercially available antacid formulations, both solid and liquid, were purchased from community pharmacies of Qassim region. The different brands of commercial antacids tablet/suspension available in the retail pharmacy shops across the Qassim region were purchased. Sodium hydroxide (NaOH), HCl and sodium carbonate used in the project were purchased from Sigma Aldrich.

Methodology

USP30/NF25 guidelines were used for the estimation of the ANC.^[24] All the tests were carried out at a temperature of 37°C ± 2°C.

Samples and reagents' preparations

0.1 M solution of hydrochloric acid

HCl (0.1 M) was made by adding 8.6 mL of 12 M HCl with water
Deionised) in 1 l volumetric flask and the volume was made up to the mark using deionised water.

0.1 M solution of sodium hydroxide

It was prepared by adding 4.0 g of NaOH in water (deionised) and the volume was made up to the mark using deionised water.

0.1 M solution of potassium hydrogen phthalate

2.04 g of potassium hydrogen phthalate (KHP) was taken in water (deionised) in 100 mL volumetric flask, dissolved and the volume was made up to the mark.

Standardisation of the solution of sodium hydroxide

0.1 M KHP (20 mL) was added into a 250 mL Erlenmeyer flask and then three drops of phenolphthalein indicator were added. Then, the solution was titrated using 0.1 M NaOH solution and the pink colour lasting for at least 30 s was taken as the endpoint. Three readings for the titration were taken and the average was taken.

Standardisation of the solution of hydrochloric acid

0.1 M HCl (20 mL) solution was added into a 250 mL Erlenmeyer flask and three drops of phenolphthalein indicator were added and the solution was titrated with 0.1 M NaOH until the endpoint which is the pink colour lasting for 30 s without fading. The titration was repeated for three times and the average titre value was recorded.

Evaluation of the acid-neutralising capacity

Antacid tablet was separately weighed and powdered. Half a gram (0.5 g) of the powdered antacid was added into a 250 mL Erlenmeyer flask and 20 mL of standardised HCl solution was added and dissolved completely. Then, three drops of bromophenol blue indicator were added into the solution. The solution turned yellow (additional 10 mL of HCl was added if the blue colour still persisted to make the solution turn yellow). Titration of the solution was performed with the standardised NaOH solution until blue endpoint (van Dop, et al., 1976 and Lin, et al., 1998), and three readings were recorded and the average reading was noted. Similarly, the procedure was repeated on all antacid formulations.

Calculation

ANC (moles of acid neutralised) = Moles of HCl added − Moles of NaOH required = (volume HCl × Molarity HCl) − (volume NaOH × Molarity NaOH).

ANC per gram of antacid = Moles of HCl neutralised/grams of antacid added

Cost-effectiveness test

Antacid needed to neutralise one mole of HCl is referred as “one equivalent,” and cost-effective antacid would be the one that cost less per equivalent.

Statistical Analysis

Statistical analyses were done using analysis of variance followed by paired t-test, and the data were presented as the mean ± standard error of mean.

Results

The study of ANC per gram of various commercial antacid brands (liquid and solid forms) sold in the community pharmacies in the Qassim region.

[Table 1]

[Figure 1]

Table 1: Acid-neutralising capacity/gram of solid and liquid antacid brands available in Qassim region

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Figure 1: The illustration presenting acid neutralizing capacity (ANC) of various solid and liquid antacid preparations available in the Qassim region. ANC: mEq (moles of acid neutralized)

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Comparison of the ANC/gram between the liquid and solid antacid preparations

[Figure 2]

Figure 2: Acid Neutralizing Capacity per gram (ANC/gram) of various solid and liquid antacid preparations available in Qassim region

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Cost-effectiveness of different commercially available antacid preparations

[Table 2]

[Figure 3]

Table 2: Cost-effectiveness of antacid preparations available in Qassim region

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Figure 3: Cost-effectiveness values of different solid and liquid dosages antacid formulations

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Discussion

Antacids are most commonly used self-medications for a whole range of gastric discomforts. Compounds commonly used in antacid formulations include magnesium hydroxide, magnesium trisilicate and Al(OH)₃. Antacids are usually a combination of Al(OH)₃ and magnesium hydroxide to maximize the buffering capabilities of each compound. Magnesium causes increased bowel motility and aluminium causes decreased motility, which is another reason why the two are usually combined. Both magnesium hydroxide and CaCO₃ have a short, rapid effect; Al(OH)₃ has a slow, persistent effect.

NaHCO₃ is a rapidly acting antacid, but it should not be used for long-term treatment in peptic ulcer disease as it is absorbed in the intestines and may cause metabolic alkalosis. The release of carbon dioxide from bicarbonate dissolved in the stomach can also be a problem as it causes belching. It is a systemic antacid because unreacted fraction of NaHCO₃ readily gains access into the general circulation and alters systemic pH. Na⁺ overload resulting from repeated use of large doses may contribute to fluid retention, oedema, hypertension, congestive heart failure and renal failure. Thus, Na⁺ overload and systemic alkalosis are some of its use limiting factors. However, this is not of clinical significance if used on an intermittent, short-term basis, but sodium bicarbonate should not be taken by patients who are on a low-salt diet. Thus, the lack of knowledge about antacids could have deleterious effects on human health, particularly, by those who tend to misuse antacids because it is easily accessible at retail pharmacy shops. In the past, studies have been carried out to determine thein vitro efficacy of antacid brands and their impact on the general population.

In our study, we evaluated ANC and the cost-effectiveness in terms of the prices of various solid and liquid antacid formulations which are commonly sold in the Qassim region. We have assessed over 11 different brands of antacid formulations, of which 5 were solid (tablet/powder) and 6 were liquid (suspension).

In the present study, we noted that the ANC of different antacid preparations varied significantly. We noted the variation in ANC between solid dosage form and also between liquid dosage forms of the antacid preparations. This was consistent from the earlier studies of Fordtran et al. who have reported 17 times differences in the potency per ml of antacids and also another study has found 10 times difference in ANC between the low and highly efficacious antacid.^[25] In this study, we observed a higher ANC/gram for the solid dosage form of the same brand compared to its liquid counterpart. For example, we observed ANC values of 13.18 and 5.62 for solid and liquid, respectively, dosage forms of Moxal plus and similarly, 8.40 and 4.5 for Moxal solid and liquid forms, respectively. Furthermore, ANC values for Gaviscon liquid and solid are 10.46 and 7.84, respectively. In the present study, the highest ANC/gram was demonstrated by solid antacid preparation, A1 (13.18), which contains Al (OH)₃, magnesium hydroxide and simethicone and the second highest ANC/gram was observed with solid antacid preparation A2 (12.72) which contains CaCO₃ and magnesium carbonate.

In the recent past, the addition of simethicone in antacids preparation has led to the resurgence in the use of antacids. Simethicone is an antifoaming agent relives discomfort from excessive gases formed in the digestive tract causing recurrent flatulence. Therefore, simethicone-containing antacids have an edge over traditional antacids in conditions where excessive gas is aggravating the symptoms in conditions such as dyspepsia, peptic ulcer, post-operative gaseous distention and irritable colon, including bloating in the upper digestive tract, pressure, fullness or feeling of stomach stuffiness.^[20]

The third highest ANC per gram was recorded with another solid antacid preparation, A4 (10.46), which contains Na-alginate, NaHCO₃ and CaCO₃.

Alginate-based antacids are another reason for an increase in the use of antacids. These antacids combine alginates which are natural polysaccharide polymers and react with gastric acid to form low-density viscous gel precipitate of near neutral pH within few seconds (in vitro) or a few minutes (in vivo). Alginate-based antacids work differently than usual antacids as it forms a protective layer and increases the viscosity and adherence of mucus to the oesophageal mucosa. In the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into foam that floats on the surface of the gastric content, providing a relatively pH neutral barrier.^[20]

In our study, we noted significantly low ANC/gram with liquid antacid preparation compared to most of the solid antacid preparations, except antacid A3 (3.48) which was an effervescent tablet. This could be attributed to the fact that chewable antacids increased surface area and therefore yielded higher ANC. Among liquid antacid preparations, the highest ANC/gram was observed with A11 (8.86) which contains sodium alginate and potassium hydrogen bicarbonate followed by A10 (7.84) containing Na-alginate, MgCO₃ and CaCO₃. It has been demonstrated earlier that the potency of antacids varies considerably among different brands of antacid preparations and is consistent from the observation of this study.^[26] Our study finding is also supported by another study by Drake and Hollander^[23] reporting difference of almost ten times in the ANC between the low and highly efficacious antacids. However, in our study, we recorded a fourfold difference in the same. Hence, from the study showing such a noticeable difference in the neutralising capability of different antacid preparations, and therefore, it is imperative that both patients and the prescribers are aware of the ANC which is being recommended and prescribed. Therefore, it is quite obvious that antacids having high ANC values were effective at the low dosage prescribed. In the present study, we used relative efficacy of antacid in terms of ANC/gram to compare efficacy of other antacids. Thus, antacid A1 having the highest ANC/gram should be effective at lower dosage volume compared to other antacids in our study.^[22]

The cost of antacid is known to influence the choice of an antacid brand beside palatability of the preparation. Further, an abundance of antacid preparations is available and many new preparations have been introduced into the market. Therefore, it is important that we are aware of the cost of a medication.^[23] In this regard, studies are carried to assess the impact of cost on the prescribing pattern of a medication which would benefit both the doctor and patient.^[26] In our study, the most cost-effective antacid preparation was A3 which is an effervescent powder. It is cheap also due to more number of pieces in a packet of the antacid. However, in terms of acid neutralization antacid preparation, A1 was found to be the most cost-effective antacid preparations followed A2. In our study, liquid antacid preparations were found to be costly in terms of their efficacy in acid neutralization. However, in general, liquid antacid preparations are prescribed because of their palatability and ease of administration.

Important factors which determine the power of an antacid preparation are their duration and onset of action, and among other acid neutralisation rate. However, the limitations of our study included failure to perform some of these factors due primarily to the time constraints and project meant for undergraduate students. The present study is anin vitro study and althoughin vitro studies could mimicin vivo environment, we know that antacid activity differs due to gastric empting, food interaction and interactions with other drugs and difference in acid secretion. Furthermore, we did not take into account differences arising from the use of the same antacid from different batches. Hence, further study is warranted to study these factors.

Conclusion

The present study is an in vitro study and although in vitro studies could mimic in vivo environment, we know that antacid activity differs due to gastric emptying, food interaction and interactions with other drugs and difference in acid secretion. Furthermore, we did not take into account differences arising from the use of the same antacid from different batches. Hence, further study is warranted to study these factors.

Ethical statement

I declare that this is a final year student research supervised by me and I have been selected by the head of department in Unaizah College of Pharmacy, Qassim University to serve as a supervisor and was submitted to the HMJ for publication.

Acknowledgement

The authors express gratitude to the management of the college for providing support in carrying out the research.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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