QbD Consideration for Developing a Double-Layered Tablet into a Single-Layered Tablet with Telmisartan and Amlodipine

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Commercially available double-layered tablets containing Telmisartan and Amlodipine (Twynstar®) present dosing convenience challenges.
• Multi-layered tablet technology, while effective, can be complex and costly to manufacture.

Purpose of the Study:

• To develop a single-layered tablet formulation of Telmisartan and Amlodipine to improve patient dosing convenience.
• To apply a Quality by Design (QbD) approach for robust formulation development and risk assessment.

Main Methods:

• A Quality by Design (QbD) methodology was employed, including risk assessments (PHA, FMEA) to identify critical material attributes (stabilizer, disintegrant) and process parameters (wet granulation, tableting).
• Central composite design was utilized to define the design space for wet granulation and tablet compression.
• Risk assessment tools identified critical material attributes and process parameters influencing formulation, drug dissolution, and impurities.

Main Results:

• The QbD approach successfully identified critical parameters and established a design space for single-layered tablet manufacturing.
• The developed single-layered tablets were bioequivalent to the original Twynstar® double-layered tablets.
• Key factors identified included stabilizer, kneading time, disintegrant, compression force, and turret speed.

Conclusions:

• A single-layered tablet formulation of Telmisartan and Amlodipine, developed using QbD, is bioequivalent to the marketed double-layered product.
• This QbD-based single-layered tablet offers improved medication compliance and serves as a platform technology for complex formulations.
• The development demonstrates a viable strategy to overcome limitations associated with multi-layered tablet manufacturing.