Double-layer tablets have two layers of active substance that are physically separate and distinguishable from each other. Layers are arranged on top of each other without mix-up and chemically reacting with another layer. 

Each layer in a bilayer tablet contains different chemical characteristics and is designed to release with different time patterns. The main advantage of the double layer is that it provides sequential release of more than one drug in a single tablet, where the active of one layer is immediately released, and the second layer takes a predetermined time for the release. 

Double-layer tablet technology has a unique advantage for pharmaceutical companies that cannot be achieved with a monolayer tablet. 

In addition to the advantages, double layer tablet has some unique challenges during their formulation development, manufacturing, and packaging. The challenges can be addressed using specialized formulation developmental techniques, operational requirements, and equipment.

Advantages of double-layer tablet

Let's discuss some advantages of double-layer tablets

More than one API in a single Dose

Bilayer tablets are a common way of administering more than one API in a single dose. Its unique design allows pharma manufacturers to provide multiple therapeutic effects with a single production process, equipment, resources, and other requirements. It also reduces the overall production cost for a pharma manufacturer due to the adoption of a single resource for various processes.

Reduced cost

Adopting more than one API in a single tablet reduces associated production costs. Because resources such as development, manufacturing, equipment, and testing process become common for more than one therapeutic effect. Additionally, a double-layer tablet also increases the marketing footprint of a pharma organization and improves revenue.

These factors and others reduce the overall production costs for a pharma organization's bilayer tablet compared to a single-layer tablet.

Stable profiles

Bilayer tablets demonstrate stable chemical and physical profiles over a long period and working conditions. They can retain their chemical and therapeutic properties under acceptable conditions, much greater than monolayer tablets. 

Another reason is that the properties of active and chemicals do not interact with each other and can only perform the desired function in the patient's stomach. It provides greater flexibility for pharma manufacturers to produce a product that can withstand different hindrance.

Coating

Like monolayer tablets, bilayer tablets can also be coated. It allows them to give their shape and desired properties according to every patient's requirements.

This is useful in cases where the resultant formulation has a bitter taste and unpleasant odor, which can affect the patient's ability to maintain regularity in drug administration.

Challenges for bilayer tablets

Bilayer tablets face unique challenges that other dosage forms do not. The main reason is that two single-layer tablets are combined in a single package. As a result, it requires special attention and care during the entire product life cycle.

Let's discuss some common challenges for bilayer tablets

Delamination

Delamination is the division of a tablet into two layers and is a common problem with a tablet of every type, and bilayer tablets are also affected by this phenomenon. There can be many stages at which delamination can occur, the most common being soon after compression and during storage in the warehouse. 

During delamination, one layer separates, and patients receive incomplete dosage, and as a result, fail to cure the disease. 

There can be many reasons for delamination; some can be attributed to formulation, material used, and equipment.

• In formulation development, the reason could be materials are not effectively tested; the process is not properly validated, or a loophole in the formulation. All these factors can degrade the binding between two different materials and cause the double-layer tablet to separate from each other.

• Table compression equipment could also be a reason for delamination in bilayer tablets. If compression force (for tablet hardness) is not appropriate according to tablet formulation requirements, the force between the two layers will be insufficient and will fail to keep both layers together. Too high a compression force will crush the bond between two layers and causes delamination in the tablets. Similarly, if the compression force is too low, it will naturally cause delamination. 

• The material used in manufacturing also affects the bonding between two layers. Delamination commonly occurs if the raw materials are sub-standards or are not according to the tablet's quality requirements. This commonly occurs if the supply chain has procured the raw material from an unapproved source or the raw material storage conditions are not according to standard, which degrades the chemical properties.

Cross Contamination 

Cross-contamination in bilayer tablets occurs when one layer intermingles with another layer. The chemical properties of a bilayer tablet are changed and can become dangerous for patients due to inappropriate release in the patient's stomach. 

Cross-contamination also occurs when chemicals from other production areas contaminate the bilayer tablet area and penetrates the equipment for processing bilayer tablet.

Inadequate compression force can also cause cross-contamination due to improper hardness, as it can cause the material of individual layers to interact freely. Suppose different stations of the compression machine are not isolated and separated. In that case, it will allow the powder of one layer to move into the station of another layer and result in cross-contamination. 

A dust collector is an effective method of collecting powder and preventing cross-contamination. It collects any airborne particles and chemicals. 

Another method is to produce tablets with adequate tablet characteristics that prevent powder from escaping the tablet and becomes effective in preventing cross-contamination. Additionally, the station of one material must be properly isolated from the stations of another material. Isolation must be verified during machine installation, qualification, and validation activities. 

Cost

Bilayer tablet is more expensive as compared to single-layer tablet. There are many associated reasons.

First, due to its unique design and advanced therapeutic effects, it costs much higher than a single-layer tablet.

The tableting machine used to produce bilayer tablets operates at low speed because the material from two hoppers is dropped in a single die in a pre-arranged manner, which takes more time to adjust. Its compression is also performed at a slower speed to allow greater impact on the powder. 

Bilayer tablet requires granulation of two tablets for each layer. The granulation is a separate process with dedicated equipment, utility supplies, and other essential requirements. Additionally, two layers require separate development, formulation, and development, increasing a bilayer tablet's expense.

So for the abovementioned challenges, it is necessary to control all the critical parameters and overcome them. Otherwise, it will affect the physical and chemical properties of individual layers in a double-layer tablet, causing to degrade the integrity of a bilayer tablet.

Double-layer tablet equipment

Double-layer tablet equipment is a tablet compression machine that can create two layers for a single tablet.

The main functions of bilayer tablets are performed by individual sub-sections designed to perform the required functions. 

Let's discuss a general layout of equipment for manufacturing double-layer equipment.

• Equipment for the bilayer tablet consists of two feed hoppers and two compression stations. The first hopper and compression station are used for the first layer, while the second hopper and compression are for the second.

• The first hopper is filled with the material of the first layer, and the second hopper is filled material of the second layer.

• When the machine starts rotating and the die passes below the first hopper, it is filled with the material from the first hopper, creating the lower layer.

• The next stage is compression, which slightly compresses the material in the die. It slightly compresses to fit the material in the die. 

• After the first compression, the die passes under the second filling station. This station creates the second layer of the bilayer tablet.

• The die then passes through the second compression stage, which presses with force to achieve the desired hardness. 

• After the second compression stage, the tablet formation process is complete and is ready to come out of the machine.

• The ejection station ejects the tablet, collected at the respective collection station.

Considerations for Double layer tablet Equipment

Let's discuss some considerations for a bilayer tablet compression machine. 

Layer Bonding: equipment for bilayer tablet compression machines must provide an effective bonding between the first and second layers. It is controlled by compression force, where the first layer is compressed with less force than the second layer. If layer bonding is not perfectly made, it will separate the two layers when ejected from the die.

Cross–Contamination: As discussed above, cross-contamination is the mixing of the material of one layer with the material of the second layer. Among many reasons, it can occur when sections between the feeding of one material and the second material are not separated, resulting in a mix-up of the two materials. It commonly occurs in feed frames and scrappers. 

Weight control: Weight control is a critical factor in bilayer tablet press machines, especially controlling the weight of individual layers. Otherwise, the output tablet will not produce the desired results. 

Output Capacity: Since a double-layer tablet press is challenging and unique, it operates at less speed and produces a low output yield. When selecting equipment for bilayer tablets, always consider your market demand. 

About the Author

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.