Biphasic pH-Responsive Delivery System: Engineering a Dual-Chambered Enteric-Coated Capsule to Neutralize Gastric Acidity While Maintaining Intestinal Homeostasis

“Antacids are systems that neutralize acids in the stomach.” (StatPearls, 2025) Magnesium hydroxide (Mg(OH)₂) is a commonly used potent antacid that provides this effect, offering strophic relief through the neutralization of stomach acids (Katzung, 2018). However, due to its strong basic nature, the lumen pH can rise above visible levels as stomach contents pass into the small intestine; this pH environment negatively affects the absorption of minerals such as iron from the exit and can reduce mineral degradation processes (O'Neil-Cutting & Crosby, 1986). Therefore, in antacid treatments, there is a delicate balance between controlling stomach acids and maintaining exit pH balance (Schinke & Karsenty, 2000). The outer capsule dissolves rapidly in the medium, facilitating the antacid distribution of Mg(OH)₂ (Katzung, 2018). The inner capsule contains a weak organic acid (citric or malic acid) and an acidic polymer matrix, and is protected by an enteric coating (Allen et al., 2011). While it is insoluble in the low pH of the medium of the enteric coating, it opens in a controlled manner at the thin outlet where the pH is ≥6 (Rowe et al., 2009). In this way, the aim is to locally balance the excessive pH increase that Mg(OH)₂ may cause (Gaitán et al., 2012). The design, which allows for the permanent range of outlet pH with antacid efficacy protection and the differentiation of the mineral absorption range, is a unique and feasible approach.