This involves using specific excipients and pH-modifying agents that create localized pH variations around API without altering the overall pH of the formulation. This can be essential for APIs sensitive to certain pH ranges or when aiming to enhance stability, solubility, or release profiles.
1. Use of pH-Modifiers as Coating Agents or Micro-Encapsulants:
Acidifying Agents: These include citric acid, fumaric acid, or tartaric acid, which can create micro-acidic environments around the API. They are used in microencapsulation processes or as part of a multi-layer tablet.
Alkalinizing Agents: Commonly used agents like sodium bicarbonate, magnesium oxide, or ammonium can create micro-basic environments when microencapsulated with the API.
These agents are embedded in a coating around the API, forming a "micro-environment" that buffers the immediate surroundings of the API.
2. Layered Tablet Formulation:
In a multi-layer tablet, different layers can be created with pH-modifying agents. For example, the core layer might contain the API with an acidifying agent, while an outer layer has buffering agents to maintain the tablet's outer surface at a neutral pH.
This allows a controlled release and stability in environments where the bulk pH is neutral, yet the API experiences a localized pH.
3. Buffered Micro-Particles:
Encapsulate the API in polymer micro-particles along with pH-modifying agents to form microenvironments. Materials like Eudragit or other enteric coatings can be used to create a micro-acidic or micro-basic environment depending on the nature of the API.
This method is common in controlled-release formulations, where you want the drug to release gradually while maintaining its stability.
4. Use of Polymers with pH-Sensitive Functional Groups:
Certain polymers, like methacrylic acid copolymers, are pH-sensitive and can create micro-environments by releasing acidic or basic ions slowly. The choice of polymer influences whether the microenvironment will be acidic or basic.
5. Inclusion of Ion-Exchange Resins:
Ion-exchange resins can be used to create a local pH by releasing ions that alter the immediate surroundings of the API. For instance, cationic resins can release acidic ions, while anionic resins can release basic ions, creating a micro-acidic or micro-basic environment.
6. Controlled Release Formulations with Osmotic Systems:
In osmotic-controlled release systems, a compartmentalized tablet can have a core containing pH-modifying agents along with the API. This method allows the creation of a microenvironment that does not affect the external medium.
When designing such systems, it’s crucial to balance the pH-modifying agent concentration and assess the potential impact on the stability and efficacy of the API. Stability studies to ensure the micro-environmental pH modification does not compromise the formulation.
Read also:
- Critical Role of API PSD in Formulation Development
- Understanding the Properties of Drug Substance During Literature Search
Resource Person: Moinuddin syed. Ph.D, PMP®
