Formulation and Therapeutic Potential of Polyherbal Effervescent Tablets Containing Glycyrrhiza glabra for the Management of Gastrointestinal Disorders: A Comprehensive Review

Digestive disorders significantly impair quality of life and frequently require long-term therapeutic management. Conditions such as gastritis, acid peptic disorders, constipation, and functional dyspepsia involve complex mechanisms including excess gastric acid secretion, mucosal damage, oxidative stress, inflammatory mediator release, and altered gastrointestinal motility (1,2). Although proton pump inhibitors, H2 blockers, and laxatives are widely prescribed, prolonged therapy has been associated with adverse effects and incomplete mucosal protection (2).

Herbal medicines provide a rational alternative due to their ability to act on multiple pathophysiological pathways simultaneously. Among these, Glycyrrhiza glabra has been extensively investigated for gastrointestinal cytoprotection. Its active constituents enhance mucus secretion, stimulate prostaglandin synthesis, inhibit inflammatory cytokines, reduce acid output, and promote epithelial regeneration (3–5). These properties position liquorice as a central therapeutic agent in digestive formulations.

Complementary herbs including Emblica officinalis, Zingiber officinale, Foeniculum vulgare, Cuminum cyminum, and Mentha piperita provide supportive antioxidant, motility-enhancing, carminative, and smooth muscle relaxant actions (6–9,11). When combined into an effervescent drug delivery system, these extracts rapidly disperse in aqueous medium, enhancing mucosal contact and therapeutic onset (10).

Extraction method of  Glycyrrhiza glabra from Liquorice roots

Liquorice roots are shade dried, pulverized, and passed through a 40-mesh sieve. For laboratory-scale hydroalcoholic extraction, 100 g of coarse powder is subjected to Soxhlet extraction using 70% ethanol for 6–8 hours at controlled temperature (60–70°C). The extract is filtered and concentrated under reduced pressure using a rotary evaporator. The semi-solid mass is dried in a vacuum oven below 50°C and stored in airtight containers. Alternatively, aqueous extraction may be performed by macerating powdered roots in distilled water for 24–48 hours followed by filtration and concentration. Hydroalcoholic extraction is generally preferred due to improved recovery of glycyrrhizin and flavonoids (5,12).

Phytoconstituents of Glycyrrhiza glabra

The pharmacological activity of liquorice is attributed to diverse bioactive compounds.

Table 1: Major Phytoconstituents of Glycyrrhiza glabra and Gastrointestinal Relevance

Effects of Liquorice in Gastrointestinal Disorders

Liquorice exerts cytoprotective effects through stimulation of mucus secretion and enhancement of prostaglandin synthesis, thereby strengthening gastric mucosal defense (3,13). Experimental studies demonstrate significant reduction in ulcer index following administration of liquorice extract (14). Anti-inflammatory properties are mediated through inhibition of cytokine production and reduction of oxidative stress (21). Deglycyrrhizinated liquorice preparations have shown clinical benefit in functional dyspepsia while minimizing mineralocorticoid-related side effects (22).

Table 2: Experimental and Clinical Evidence of Liquorice in GI Disorders

Effects of Polyherbal Ingredients on Gastrointestinal Passage

The supportive herbs included in the formulation influence gastric emptying, intestinal motility, and mucosal comfort.

Table 3: Effects of Herbal Ingredients on Gastrointestinal Passage

Rationale for Selecting Effervescent Tablets or Granules

Effervescent tablets or granules were selected to enhance the therapeutic performance of the proposed polyherbal gastrointestinal formulation. Gastrointestinal disorders such as gastritis, dyspepsia, and acid peptic disease involve mucosal irritation, oxidative stress, inflammation, and altered motility (1,2). Effervescent systems rapidly disintegrate in water, ensuring immediate dispersion of active constituents and faster onset of action compared to conventional solid tablets (10). Pre-dissolved administration improves mucosal contact, which is particularly beneficial for cytoprotective agents such as Glycyrrhiza glabra, known to stimulate mucus secretion, enhance prostaglandin synthesis, and reduce inflammatory damage (3,13,14). In addition, effervescent delivery improves palatability and compliance, especially when administering herbal extracts with strong taste profiles (10). Rapid availability of antioxidant and anti-inflammatory phytoconstituents such as glycyrrhizin, flavonoids, and chalcones may contribute to improved mucosal protection and reduction of oxidative injury (3,5,19). Thus, effervescent technology complements the pharmacological actions required for effective gastrointestinal management.

Reasons for Limited Development of Similar Effervescent Polyherbal Formulations

Despite strong evidence supporting the anti-ulcer and cytoprotective effects of liquorice (3–5,14), effervescent polyherbal gastrointestinal products remain uncommon. One major limitation is formulation complexity. Effervescent systems are highly moisture sensitive and require controlled manufacturing conditions and protective packaging to maintain stability (10). Herbal extracts contain multiple phytoconstituents whose stability may vary under acidic effervescent conditions (19). Standardization also presents challenges, as therapeutic efficacy depends on consistent glycyrrhizin content and extract quality (3,12). Although deglycyrrhizinated liquorice has shown clinical benefit in functional dyspepsia (22), incorporation into stable effervescent systems requires careful compatibility and stability evaluation. These pharmaceutical constraints likely explain the limited commercialization of such formulations.

Comparison with Marketed Gastrointestinal Formulations

Conventional gastrointestinal therapies such as proton pump inhibitors and H? blockers provide acid suppression but may not fully address oxidative stress or mucosal repair mechanisms (2). In contrast, Glycyrrhiza glabra demonstrates significant ulcer reduction and cytoprotection through mucus enhancement and anti-inflammatory activity (3,14). Its flavonoids also exhibit antioxidant and anti–Helicobacter pylori effects (5,16,17). Supportive herbs further enhance therapeutic breadth. Phyllanthus emblica provides antioxidant gastroprotection (4,6), Zingiber officinale improves gastric motility (7), Foeniculum vulgare relieves bloating (8), Cuminum cyminum stimulates digestion (9), and Mentha piperita exerts antispasmodic effects (11). Unlike synthetic effervescent antacids that mainly neutralize acid, the proposed polyherbal effervescent formulation offers rapid dispersion combined with multi-targeted mucosal protection, antioxidant support, and motility regulation (1,3,5,10).

Effervescent Drug Delivery: Advantages and Limitations