Advantages and Challenges of Bilayer Tablet Dosage Forms

Bilayer tablets have gained increasing attention in recent years as an innovative and effective oral solid dosage form. By incorporating two distinct layers within a single tablet, this formulation offers numerous advantages that cater to complex therapeutic needs and patient convenience. This article provides a comprehensive overview of bilayer tablets, highlighting their key applications, benefits, formulation challenges, and notable commercial examples.

Introduction 

Bilayer tablets are a specialized form of oral solid dosage where the tablet is designed with two separate layers. These layers may be composed of the same or different active pharmaceutical ingredients (APIs). The dual-layer design allows for tailored drug release, improved patient compliance, and enhanced formulation stability. The development of bilayer tablets is guided by several key objectives, each addressing specific clinical or formulation needs:

• Fixed-dose combination – FDC: Combining two or more drugs in a single tablet simplifies treatment regimens and enhances patient compliance. FDCs are increasingly common in chronic disease management, including type 2 diabetes, hypertension, pain, and HIV/AIDS. Examples: Coveram (Perindopril/Amlodipin), Janumet (Metformin/Sitagliptin)…
• Controlled Drug Release: One layer can provide immediate release (IR) for a rapid onset of action, while the other offers sustained release (SR) to maintain therapeutic levels over time—particularly useful for a loading dose followed by maintenance. Examples: Janumet XR (Sitagiptin IR/Metformin XR), Xigduo XR (Dapagliflozin IR/Metformin XR)…
• Separation of Incompatible Ingredients: Chemical or physical incompatibilities during storage can be mitigated by isolating APIs in separate layers. Examples: Roszet (Rosuvastatin/Ezetimib), Exforge (Amlodipin/Valsartan)…
• Improved Tablet Design: Layer differentiation by color enhances visual recognition and consumer experience.
• Product Lifecycle Extension: Bilayer tablet technology offers opportunities for new product development and lifecycle management of existing therapies.

Challenges in Designing Bilayer Tablets

Despite their promising potential, bilayer tablets also pose several formulation and manufacturing challenges. Addressing these challenges is critical for ensuring product quality, regulatory compliance, and therapeutic efficacy:

• • Physicochemical Properties of Materials: Variability in flowability, compressibility, particle size, and moisture content between layers can affect processability and mechanical strength.
  • Compression Forces: The force applied to each layer influences interfacial bonding and tablet integrity. Inadequate compression may lead to delamination or capping.
  • Lubricant Selection: The choice and use of lubricants must be optimized to avoid compromising interlayer adhesion and dissolution performance.
  • Layer Ratio and Sequence: The relative mass and compression order of each layer affect uniformity and overall tablet strength. Compressing a lighter layer first can be technically challenging with conventional equipment.
  • Environmental Conditions: Humidity and temperature during manufacturing and storage can impact mechanical properties and interfacial strength, especially with hygroscopic materials.
  • Layer Weight Control: Accurately controlling the weight of individual layers—particularly the second layer—is difficult due to limitations in real-time monitoring and sampling technologies.
  • Interfacial Characteristics: The surface roughness and properties of the first layer influence adhesion with the second layer, affecting overall structural integrity.
  • Tablet Press Equipment: Selecting a bilayer tablet press with suitable features such as force control, weight regulation, and appropriate dwell time is essential for consistent, high-quality production

Bilayer tablets offer a forward-looking solution in pharmaceutical dosage design, capable of addressing increasingly complex treatment needs. They enhance therapeutic efficacy, improve patient compliance, and support the development of innovative or lifecycle-managed products. While the formulation and manufacturing processes involve a range of technical challenges, continued advancements in pharmaceutical technologies and tablet press equipment are making it increasingly feasible to produce high-quality bilayer tablets at scale.

With their ability to combine multiple APIs, optimize drug release profiles, and improve treatment outcomes, bilayer tablets are set to play a central role in the future of oral drug delivery systems.

References

Review of bilayer tablet technology