A Review on Phytopharmaceutical Effervescent Tablet: A Green Approach to Gastric Acid Neutralization

Abstract

Effervescent tablets are specialized oral dosage forms designed to rapidly produce carbon dioxide upon contact with water, resulting in quick dissolution and enhanced drug absorption. Typically prepared by compressing active ingredients with effervescent agents such as citric acid and sodium bicarbonate, these tablets offer fast onset of action and improved patient compliance compared to conventional forms. Effervescent antacid tablets, in particular, are formulated to provide prompt relief from acidity and indigestion by ensuring rapid disintegration and superior bioavailability. Increasing interest in herbal medicine has led to the incorporation of natural acid suppressants like licorice, amla, fennel, and clove into effervescent formulations, combining traditional knowledge with modern technology for safer and more effective therapy. Acidity and peptic ulcers are common gastrointestinal disorders resulting from excessive secretion of gastric acid, often linked to Helicobacter pylori infection or overstimulation of parietal cells, leading to mucosal damage. Although several synthetic antacids and antiulcer drugs are available, many cause adverse effects with prolonged use. Consequently, herbal alternatives are gaining attention due to their safety, efficacy, affordability, and holistic healing potential. The objective of herbal effervescent antacids is to neutralize gastric acid, promote mucosal protection, and alleviate symptoms such as pain and burning sensation in the oesophagus. This review highlights the formulation aspects, pharmacological properties, and evaluation parameters of herbal effervescent antacid tablets, while providing an overview of the herbal plants commonly employed for the management of acidity and peptic ulcers, along with their pharmacological activities and plant parts used.

Keywords

Introduction

Gastric acid-related disorders including gastroesophageal reflux disease (GERD), dyspepsia, heartburn and peptic ulcer disease (PUD) remain highly prevalent worldwide and are a major cause of morbidity and health-care utilization. Recent global analyses report substantial and regionally variable prevalence of GERD and PUD, with millions affected and persistent disease burden driven by factors such as Helicobacter pylori infection, non-steroidal anti-inflammatory drug (NSAID) use, tobacco, alcohol, and dietary/lifestyle contributors. [1,2] Phytopharmaceuticals standardized plant extracts or plant-derived active constituents developed with pharmaceutical rigor offer the potential to complement or partially replace conventional mineral antacids. Numerous medicinal plants and their phytochemicals (for example, Glycyrrhiza glabra, Emblica officinalis, Zingiber officinale, Musa spp. and several flavonoids and tannin-rich botanicals) show gastroprotective, mucoprotective, antioxidant and anti-Helicobacter activities in preclinical and some clinical studies; these properties may help restore mucosal defense, reduce oxidative injury and modulate ulcer healing in addition to buffering acid. Systematic reviews summarize a broad preclinical evidence base for phytochemicals with anti-ulcer activity, although the degree of clinical evidence varies and standardization remains a key requirement. [3,4]

2. Gastric Acid & Neutralization:

2.1 Gastric Acid Secretion

Gastric acid is secreted primarily as hydrochloric acid (HCl) by the parietal cells of the gastric mucosa. The secretion is tightly regulated by acetylcholine (via vagus nerve), gastrin (from G-cells), and histamine (from enterochromaffin-like cells), which stimulate the H?/K?-ATPase proton pump at the apical surface of parietal cells. This mechanism maintains an intragastric pH as low as 1.0–2.0, essential for food digestion, activation of pepsinogen to pepsin, and defense against ingested microbes [5,6]

2.2 Pathological Acid Secretion

Hypersecretion of gastric acid, combined with weakened mucosal defense, can lead to acid-peptic disorders such as gastroesophageal reflux disease (GERD), gastritis, peptic ulcer disease, and dyspepsia. Risk factors include Helicobacter pylori infection, chronic use of NSAIDs, stress, alcohol intake, and smoking. These conditions are characterized by abdominal pain, epigastric burning, bloating, and discomfort [7,8].

2.3 Neutralization of Gastric Acid

Antacids are agents that directly neutralize gastric HCl, elevating gastric pH from highly acidic (pH 1–2) to a safer level (pH 3–4). This:

• Inactivates pepsin, which becomes inactive at pH >4.
• Provides rapid symptomatic relief in acidity and heartburn.
• Creates a favorable environment for healing of gastric and duodenal ulcers.

The neutralization reaction typically produces water, salts, and carbon dioxide (if carbonate/bicarbonate is present). Example:

CaCO? + 2HCl → CaCl? + H?O + CO?↑\text{CaCO? + 2HCl → CaCl? + H?O + CO?↑}CaCO? + 2HCl → CaCl? + H?O + CO?↑

Systemic Vs Non-Systemic Neutralization

• Systemic antacids (e.g., sodium bicarbonate, calcium carbonate) are absorbed into the bloodstream, may cause systemic alkalosis and have shorter action.
• Non-systemic antacids (e.g., magnesium hydroxide, aluminum hydroxide) act locally in the stomach without systemic absorption but may lead to diarrhoea or constipation as side effects [9,10].

3. Phytopharmaceuticals And Their Role In Gastric Acid Neutralization:

Phytopharmaceuticals are standardized plant-derived medicines that contain active phytoconstituents responsible for specific pharmacological effects. Unlike crude herbal extracts, phytopharmaceuticals undergo scientific validation, quality control, and standardization similar to modern drugs. Their growing popularity in gastrointestinal disorders, particularly in managing gastric acid-related issues, is due to their safety, efficacy, and minimal side effects compared to conventional antacids and proton pump inhibitors. [11,12,13]

3.1 Mechanism of Gastric Acid Neutralization

Gastric acid is primarily composed of hydrochloric acid (HCl) secreted by parietal cells in the stomach. Excessive acid secretion or reduced mucosal defense leads to conditions such as gastritis, acid reflux, and peptic ulcers. Phytopharmaceuticals neutralize or regulate acid levels through:

• Direct acid neutralization by alkaline constituents (e.g., carbonates, flavonoids).
• Mucosal protection via increased mucus and bicarbonate secretion.
• Antioxidant and anti-inflammatory actions, reducing gastric mucosal damage.
• Inhibition of H?/K?-ATPase enzyme, similar to proton pump inhibitors. [11,12,13]

4. Phytopharmaceutical Rationale:

4.1 Need for a Green Approach

Conventional antacids, though effective, are associated with several drawbacks such as constipation, diarrhoea, rebound hyperacidity, altered mineral absorption and systemic alkalosis with prolonged use. Furthermore, long-term use of proton pump inhibitors (PPIs) and H? receptor antagonists has been linked with hypomagnesemia, renal complications, gut microbiota imbalance, and increased risk of infections [14,15]. This highlights the need for safer, natural alternatives that provide acid neutralization along with mucosal protection and fewer side effects.

4.2 Phytopharmaceutical Advantages

Phytopharmaceuticals, derived from medicinal plants, are increasingly explored as a green, sustainable, and biocompatible option for managing gastric acid-related disorders. The rationale is based on:

Natural Antacid & Cytoprotective Action: Many herbal extracts (e.g., Glycyrrhiza glabra, Aloe vera, Mentha piperita, Zingiber officinale) exhibit buffering effects and stimulate mucous secretion, strengthening gastric defense [16,17].

Synergistic Activity: Phytoconstituents such as flavonoids, tannins, saponins, and alkaloids not only reduce acidity but also possess anti-inflammatory, antioxidant, and antimicrobial properties, providing holistic protection against H. pylori and oxidative damage [18].

5. Herbal Candidates for Effervescent Antacid Formulation

1. Glycyrrhiza glabra (Licorice) – Mucoprotective

Licorice root contains glycyrrhizin and flavonoids that stimulate mucus secretion, enhance gastric mucosal defense, and inhibit acid secretion. It forms a protective layer on the gastric mucosa, preventing ulceration and acid-induced injury. It has been traditionally used for gastritis and peptic ulcer management [19].

Figure 1: Glycyrrhiza Glabra (Liquorice)

2. Emblica officinalis (Amla) – Antioxidant

Amla fruit is rich in ascorbic acid, tannins and polyphenols. It exhibits strong antioxidant activity, scavenging reactive oxygen species (ROS) generated during acid-induced gastric mucosal damage. Clinical studies show that it reduces gastric acidity and promotes ulcer healing by protecting against oxidative stress [20].

Figure 2: Emblica Officinalis (Amla)

3. Musa paradisiaca (Banana) – Antacid Activity

Banana fruit pulp contains pectin, flavonoids, and sterols that exhibit significant acid-neutralizing capacity and gastroprotective action. Extracts of ripe banana have been shown to increase mucin secretion and reduce gastric acidity, making it a natural antacid candidate [21].

Figure 3: Musa Paradisiaca (Banana)

4. Zingiber officinale (Ginger) – Gastroprotective

Ginger rhizome contains gingerols and shogaols, which have potent anti-inflammatory and antioxidant activities. It improves gastric emptying, reduces nausea, and protects the gastric mucosa against ethanol- and stress-induced ulcers. Its gastroprotective role is linked to increased prostaglandin secretion and free radical scavenging [22].

Figure 4: Zingiber Officinale (Ginger)

6. Effervescent Tablet Technology:

Effervescent tablets are solid dosage forms that rapidly disintegrate in water, releasing carbon dioxide gas to form a sparkling solution. This unique mechanism not only enhances the palatability and aesthetic appeal of oral medications but also improves bioavailability and patient compliance. In the pharmaceutical industry, effervescent technology has gained significance for delivering both allopathic and phytopharmaceutical actives, especially in formulations designed for rapid action such as gastric acid neutralizers, vitamin supplements, and analgesics. Effervescence offers an eco-friendly and patient-friendly alternative by eliminating the need for swallowing tablets or capsules an especially valuable feature for paediatric and geriatric populations. [23,24,25]

6.1 Principle of Effervescent Tablet Technology:

Effervescent tablets are based on a chemical reaction between acids and bases in the presence of water, producing carbon dioxide (CO?) that facilitates disintegration and dissolution. [23,24,25]

Figure 5: Effervescent Tablet

7. Digital & AI in Development of Phytopharmaceutical Effervescent Antacid Tablets:

7.1 Computer-Aided Formulation Design (CAFD):

Artificial intelligence (AI) and machine learning (ML) models can predict optimal combinations of acids, bases, and excipients for effervescent systems. By integrating design of experiments (DoE) with AI algorithms, formulation scientists can reduce trial-and-error, saving time and resources. [26]

7.2 Digital Twin Technology:

A digital twin (virtual replica) of the manufacturing process can simulate the effects of moisture, compression force, and granulation methods on tablet stability. This allows proactive adjustments in process parameters before scaling-up. [27]

7.3 AI-driven Phytochemical Profiling:

AI-assisted spectroscopic analysis (FTIR, NMR, HPLC fingerprints) can rapidly identify and quantify bioactive markers in Glycyrrhiza, Emblica, Musa, and Zingiber extracts. Machine learning models enhance accuracy in herbal standardization, ensuring batch-to-batch consistency. [28].

CONCLUSION:

Phytopharmaceutical-based effervescent tablets represent an innovative and eco-friendly alternative for gastric acid neutralization. By integrating herbal actives with effervescent technology, this green formulation approach not only ensures rapid relief from acidity but also minimizes the side effects associated with conventional synthetic antacids. The use of natural ingredients enhances patient compliance, biocompatibility and sustainability. Overall, phytopharmaceutical effervescent tablets mark a promising step toward safer, more effective, and environmentally responsible gastric acid management.                                          

REFERENCE

1. Nirwan JS, et al. Insight into global burden of gastroesophageal reflux disease. (systematic review).  https://pmc.ncbi.nlm.nih.gov/articles/PMC11907340/
2. Lu S, et al. The global, regional and national burden of peptic ulcer disease. https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-022-02130-2
3. Hamid A, et al. Plants and phytochemicals for treatment of peptic ulcer: https://www.sciencedirect.com/science/article/pii/S0254629920312205
4. Asl MN, et al. Antiulcer properties of Glycyrrhiza glabra L. (experimental evidence for licorice). https://pmc.ncbi.nlm.nih.gov/articles/PMC4673944/
5. Singh P, Chaturvedi R, Asim M. Physiology of gastric acid secretion and regulation. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK541037/
6. Allen A, Flemström G. Gastric mucosal protection and acid secretion. Physiol Rev. 2005;85(2):975-1004.
7. Malfertheiner P, Chan FKL, McColl KEL. Peptic ulcer disease. Lancet. 2009;374(9699):1449-1461. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60938-7/abstract
8. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017;112(2):212-239. https://journals.lww.com/ajg/fulltext/2017/02000/acg_clinical_guideline__treatment_of_helicobacter.12.aspx
9. Kaul A, Ghosh A, et al. Antacids revisited: contemporary facts and clinical relevance. J Basic Clin Physiol Pharmacol. 2021;32(6):1059-1070.
10. Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases. N Engl J Med. 1990; 323:1672-1680. https://www.nejm.org/doi/full/10.1056/NEJM199012133232407
11. Borrelli, F. & Izzo, A.A. (2000). The plant Licorice (Glycyrrhiza glabra L.): New uses for an old herb. Phytotherapy Research, 14(8), 579–585.
12. Langmead, L. et al. (2004). Aloe vera gel in the treatment of irritable bowel syndrome: A randomized controlled trial. Alimentary Pharmacology & Therapeutics, 19(5), 521–527.
13. Mascolo, N. et al. (1989). Biological characterization of Zingiber officinale extract. Journal of Ethnopharmacology, 27(1-2), 129–140.
14. Reimer C. Safety of long-term PPI therapy. Best Pract Res Clin Gastroenterol. 2013;27(3):443-454. https://www.sciencedirect.com/science/article/abs/pii/S1521691813001121?via%3Dihub
15. Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology. 2017;153(1):35-48 https://www.gastrojournal.org/article/S0016-5085(17)35623-8/fulltext
16. Borrelli F, Izzo AA. The plant kingdom as a source of anti-ulcer remedies. Phytother Res. 2000;14(8):581-591.
17. Khare CP. Indian Medicinal Plants: An Illustrated Dictionary. Springer, 2007.
18. Rafatullah S, et al. Evaluation of natural products in peptic ulcer disease. Saudi J Gastroenterol. 2014;20(3):150-158.
19. Borrelli F, Izzo AA. The plant kingdom as a source of anti-ulcer remedies. Phytother Res. 2000;14(8):581–591.
20. Sairam K, et al. Antacid and antiulcer activities of Emblica officinalis Gaertn. J Ethnopharmacol. 2002;82(2-3):1–9.
21. Goel RK, Sairam K. Anti-ulcer drugs from indigenous sources with emphasis on Musa sapientum, tamrabhasma, Asparagus racemosus and Zingiber officinale. Indian J Pharmacol. 2002; 34:100–110. https://journals.lww.com/iphr/pages/default.aspx
22. Al-Yahya MA, et al. Gastroprotective effect of ginger (Zingiber officinale Roscoe) against ethanol-induced gastric mucosal injury in rats. J Ethnopharmacol. 2016; 210:75–82. https://www.sciencedirect.com/science/article/abs/pii/S0378874116302744?via%3Dihub
23. Bhandari, N. & Jain, A. (2020). Effervescent tablets: A promising approach for oral drug delivery. Journal of Drug Delivery and Therapeutics, 10(3), 189–194.
24. Nanda, A., Kandarapu, R., & Garg, S. (2002). An update on taste masking technologies for oral pharmaceuticals. Indian Journal of Pharmaceutical Sciences, 64(1), 10–17.
25. Chaturvedi, A.K. et al. (2013). Effervescent tablet: A comprehensive review. International Journal of Pharmaceutical Sciences and Research, 4(7), 2641–2652.
26. Yu LX, et al. Modernizing pharmaceutical manufacturing: from batch to continuous production. J Pharm Innov. 2022; 17:1–12.
27. Srai JS, et al. Digital Twins: Applications to Pharmaceutical Manufacturing. Int J Pharm. 2022; 613:121399.
28. Liang YZ, et al. Quality control of herbal medicines using chemometric techniques and artificial intelligence. J Chromatogr B. 2021; 1169:122609. https://www.sciencedirect.com/science/article/abs/pii/S1570023221000891?via%3Dihub.