Messi Biology of Hebei Province states that magnesium oxide plays an indispensable role as a “key excipient” in oxytetracycline water-based injections (injectable solutions). Through chelation, it effectively solves the two core technical challenges of low oxytetracycline solubility and chemical instability. It is the core reason why oxytetracycline can be made into a stable, effective, and usable injectable dosage form. This is a very classic and crucial pharmaceutical application, with its core function being to improve the solubility of oxytetracycline and the stability of the solution.
Core Role: Chelation and Solubilization
Inherent Properties of Oxytetracycline that Present Challenges:
- Low Solubility: Oxytetracycline itself is an amphoteric compound, but its free acid form has very poor solubility in water, making it impossible to directly produce high-concentration water-based injections.
- Chemical Instability: Oxytetracycline is very unstable in acidic or neutral aqueous solutions and is prone to degradation, leading to reduced efficacy and potentially generating toxic byproducts.
The Role of Magnesium Oxide – Chelating Agent:
- Magnesium oxide (MgO) forms magnesium hydroxide Mg(OH)₂ in water, providing magnesium ions (Mg²⁺).
- The oxytetracycline molecule contains multiple phenolic hydroxyl and enol groups, which can undergo strong chelation reactions with magnesium ions (Mg²⁺) to form a stable, water-soluble oxytetracycline magnesium complex.
Increasing Solubility:
- The resulting oxytetracycline magnesium complex is hydrophilic, and its solubility in water is much greater than that of oxytetracycline itself. This makes it possible to prepare high-concentration injectable solutions (such as the common 5%, 10%, and 20% concentration oxytetracycline injections).
Enhancing Stability:
- Chelation “locks” the active groups in the oxytetracycline molecule that are prone to degradation reactions, thereby greatly slowing down its decomposition rate in solution and extending the drug’s shelf life.
- The resulting complex solution is usually alkaline (pH about 8-9.5), which also favors the stability of oxytetracycline.
Reducing Local Irritation:
- High-concentration oxytetracycline solutions themselves have a strong irritant effect on muscle tissue, which can cause pain, swelling, and even necrosis at the injection site.
- After the formation of the complex, the properties of the solution become milder, which to some extent reduces the irritation of intramuscular injection.
Brief Description of the Preparation Process:
- First, mix magnesium oxide with oxytetracycline powder and grind with a small amount of water or solvent to allow it to fully chelate.
- Then add other excipients (such as procaine, antioxidants, solubilizers, etc.).
- Finally, add water to the full volume, adjust the pH to a stable range (usually 8.0-9.5), filter, fill, and sterilize.