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Tablets & Capsules March/April 2021 32C membrane of the esophagus, leading to inflammation, preliminary stages of cancer (Barrett's esophagus), ulcers, bleeding, and esophagus strictures due to scarred tissue. The prevalence of acid reflux, as well as its short- and long- term health consequences, make it necessary to formulate effective drug products. Physiological Background Gastric juice mainly contains water, hydrochloric acid, pepsinogen, mucus, and bicarbonate. These components break down, denature, and disinfect ingested food. Due to its hydrochloric acid content, the pH of gastric juice under fasted conditions lies in the range of 1 to 1.5 [3]. In healthy people, the lower esophageal sphincter mus- cle prevents the reflux of acidic gastric content into the esophagus. However, certain functional disorders may lead this closure mechanism to fail. Organic causes as well as nutritional and lifestyle habits—such as excessive consumption of alcohol, nicotine, or caffeine; severe obe- sity; and psychological stress—can trigger or aggravate reflux-related health issues [1, 4, 5]. Medical treatments The acidity of gastric fluid can be reduced by pro- ton-pump inhibitors (PPls), such as lansoprazole, omeprazole, and esomeprazole, or by administration of mild basic sub- stances. The latter have a very rapid, but short-term action. In fact, the strong reduction in stomach acidity often leads to a rebound effect, which aggravates the situation. PPls, on the other hand, enable a mild, long-term adjustment of the gastric fluid's pH, making them a popular choice for chronic acid reflux sufferers. There is, however, increasing concern about the possible side effects of PPls, including an increased risk of gastric neoplasia, kidney disease, bone fractures, impaired absorption of micronutrients, dementia, and liver disease [6]. Alginate-based anti-reflux preparations, by contrast, work by forming a protective layer in the stomach that acts as a mechanical barrier, preventing reflux into the esophagus. Alginates are salts of naturally occurring alginic acid, a major structural component in the cell walls of brown algae. After extracting alginic acid from seaweed, sodium or cal- cium chloride is added to precipitate the alginate salt [7]. While sodium alginate is water-soluble, calcium alginate and alginic acid form gels in water. These gels form a pro- tective layer, or raft, in the stomach, which floats on the surface of the gastric fluid and prevents reflux of gastric acid into the esophagus, as shown in Figure 1. Flotation is achieved when carbon dioxide bubbles embed into the gel layer. Both alginic acid and calcium alginate are able to form protective rafts (Figures 2, 3). Over-the-counter medicines containing alginates have been used for the symptomatic treatment of heartburn for more than 50 years and have a positive track record in terms of efficacy and safety [8]. Figure 3 Formation of calcium alginate raft Gastric Acid Sodium Alginate Calcium Carbonate Calcium Alginate Gel CO 2 Gas Calcium Alginate Raft Figure 2 Formation of alginic acid raft Gastric Acid Sodium Bicarbonate Sodium Alginate Alginic Acid Gel CO 2 Gas Alginic Acid Raft Table 1 Example anti-reflux formulation with sodium alginate (Vivapharm PH R5) Ingredient [g/100 mL] Sodium alginate 5 Water (deionized) for dissolving the alginate 70 Sodium bicarbonate 2.13 Calcium carbonate 3.25 Flavor q.s. Preservative q.s. Water (deionized) for pre-dissolving further ingredients and volume adjustment q.s. Figure 1 Calcium alginate raft preventing reflux of gastric acid into the esophagus Sodium Alginate Calcium Carbonate Gastric fluid Acid reflux Protective raft