Messi Biology states that magnesium oxide (MgO) plays a crucial role in protecting the stability of omeprazole enteric-coated tablets, including:
- Neutralizing acidity and preventing hydrolysis
- Maintaining stable pH within the tablet core
- Reducing the risk of oxidative degradation
In pharmaceutical formulation design, the rational use of magnesium oxide can not only extend the shelf life of the drug but also improve its performance consistency and therapeutic stability in the gastrointestinal environment.
I. The Instability Issues of Omeprazole
- Acid Instability: Omeprazole, a proton pump inhibitor, is highly susceptible to degradation in acidic environments, especially under gastric fluid conditions with a pH < 4, where it almost completely decomposes.
- Hydrolytic Sensitivity: Even under neutral or slightly alkaline conditions, omeprazole can undergo hydrolytic deactivation if trace amounts of moisture are present.
- Need for Special Coating Protection: To prevent degradation in the stomach, omeprazole must be administered in an enteric-coated formulation, allowing it to bypass gastric acid and be dissolved and absorbed directly in the small intestine.
II. The Stabilization Mechanism of Magnesium Oxide
- Alkaline Microenvironment Modulation: Magnesium oxide is a typical basic oxide that can release Mg²⁺ and OH⁻ ions, significantly increasing the pH of the microenvironment.
Introducing magnesium oxide into the omeprazole tablet core can create a stable alkaline buffer at the microscopic level, preventing acidic hydrolysis caused by coating damage or moisture. - Protecting Active Ingredients from Gastric Acid Attack: Even if the enteric coating has localized micropores or microcracks, magnesium oxide can neutralize any infiltrating acidic moisture, acting as a “secondary protective barrier” and slowing down the degradation rate of omeprazole.
- Inhibiting Oxidation Reactions and Free Radical Generation: The omeprazole structure contains sulfoxide groups that are easily oxidized. Magnesium oxide has an antioxidant buffering effect to a certain extent, reducing the attack of reactive oxygen species on the drug.
III. Application Strategies in Formulation Design
- Combined Use with Other Alkaline Substances: Magnesium oxide is often used in combination with sodium bicarbonate, aluminum hydroxide, and other substances to jointly regulate the pH value within the tablet core or under the coating.
The proportion of magnesium oxide can be adjusted based on drug stability data to achieve the best protective effect. - Use in Double-Layer or Three-Layer Structures: In some innovative enteric-coated tablets, magnesium oxide is designed as an intermediate protective layer or buffer layer located between the drug core and the enteric coating, enhancing the overall barrier performance.
IV. Actual Stability Improvement Effects
Experimental data show that the content of omeprazole enteric-coated tablets without magnesium oxide decreases significantly within 6 months under 40°C/75% RH conditions, while the retention rate of active ingredients increases by more than 20% after adding an appropriate amount of magnesium oxide.
Samples with magnesium oxide also showed smaller batch-to-batch differences and higher drug release integrity in in vitro release tests.