INTRODUCTION:

Compared bilayer tablets the conventional monolayer tablets, has a few significant benefits. For example, by physically separating formulation components, these tablets are frequently employed to prevent chemical incompatibilities. By combining layers with different release patterns or slow-release with immediate-release layers, bilayer tablets have also made it possible to design controlled administration of active medicinal components with predefined release profiles.¹ A bi-layer tablet can be used to segregate two substances that are incompatible, release two medications in combination in a sequential manner, or create a sustained release tablet where the first layer releases the first dose immediately and the second layer performs maintenance.²

Because oral consumption is the most convenient and widely used method of drug delivery, it is also the easiest to administer. It is commonly known that compared to immediate release medication formulations, sustained release dosage forms may have one or more effect.

When the high cardiac output puts pressure on the artery wall as blood flow increases, hypertension, or high blood pressure, results. Because the current standard dosage form used to treat hypertension cannot achieve the intended therapeutic impact for a greater period of time, there is a higher risk of dose fluctuation and missed doses.³

ADVANTAGES:⁴

· Unit dosage forms are the most effective oral dosage forms available, providing the highest level of dose accuracy and the least amount of content variability.

· It is less expensive than any other oral dose type.

· Smaller and lighter.

· Boosting stability and enabling the application of characterisation instruments that aren't feasible in bulk solutions.

· Coating technique can hide unpleasant odour and bitter taste.

· Simple to swallow and least likely to cause hang-ups.

DISADVANTAGES:⁶

· Certain medications are amorphous and low density, making them resistant to compaction into dense compacts.

· It may be necessary to cover or encapsulate medications that are sensitive to oxygen, have an unpleasant odour, or are bitter test substances.

· Difficult to swallow when a patient is unconscious or a youngster.

· It must have a shelf life that is chemically stable to prevent changes to the therapeutic agents.

· Drugs that are difficult to synthesize or manufacture as tablets that will nevertheless give acceptable or complete drug bioavailability are those with poor wetting, slow dissolving characteristics, and optimal absorption high in the gastrointestinal tract.

· It is physical characteristics ought to be preserved over time by having the necessary chemical and physical stability. The bi-layer tablet must be able to release the therapeutic ingredients in a predictable and reproducible way.

NEED OF BILAYER TABLETS⁷:

· The objective is to isolate incompatible active pharmaceutical ingredients (APIs) from one another and regulate the API release from a layer by exploiting the functional feature of a different layer.

· To establish erodible/swellable barriers for modified release by either sandwiching one or two active layers between them to change the overall surface area available for the API layer.

· Regulating the pace at which one or two distinct active medicinal components are delivered.

· To provide fixed dose combinations of various APIs, extend the life of drug products, develop novel drug delivery methods such chewing devices and floating tablets for gastro-retentive drug delivery, and develop buccal/mucoadhesive delivery systems.

Quality and Good manufacturing practice (GMP) requirements of bi-layer tablets

In order to manufacture a high-quality, approved, and GMP bi-layer tablet, the chosen press must be able to:

· Keeping the two separate layers that make up the bi-layer tablet from capping and separating.

· Providing an adequate level of tablet hardness.

· Keeping the two layers from becoming contaminated with each other.

· Resulting in the two layers visual separation becoming evident.

· High yield.

· Precise weight control for each of the two layers.

CHALLENGES IN BILAYER: MANUFACTURING⁹:

Conceptually, bilayer tablets can be seen as two

Single - layer tablets compressed into one. In Practice,

there are some manufacturing challenges.

Delamination:

When the tablet's two halves don't fully adhere to one another, the tablet breaks. When crushed, the two granulations ought to stick together.

Cross-contamination:

Cross-contamination happens when the granulation of the first layer mixes with the granulation of the second layer, or the other way around. It might even defeat the dual-layer tablet’s original intent. One of the most effective ways to avoid cross-contamination is through proper dust collection.

Production yields:

Dust collection is necessary to prevent cross-contamination, which results in losses. Bilayer tablets yield less than single-layer tablets as a result.

Cost:

For a number of reasons, bilayer tableting is more expensive than single layer tableting. Firstly, the tablet press is more expensive. Second, in bilayer mode, the press often operates more slowly. Third, additional time must be spent on formulation creation, analysis, and validation in order to create two compatible formulations. These variables will affect the bilayer compression itself and the quality characteristics of the bilayer tablets (enough mechanical strength to preserve its integrity and individual layer weight management) if they are not properly managed or adjusted. Consequently, in order to enable the creation of a resilient product and process, it is imperative to get insight into the underlying reasons.

TYPES OF BILAYER TABLET PRESS^10,11

· Single sided tablet press.

· Double sided tablet press

· Bilayer tablet press with displacement

· Monitoring.

Single sides press:

A single-sided press with the doublet feeder's two chambers kept apart is the most basic design. The two distinct tablet levels are created by either gravity or force feeding each chamber with varying strengths. The first layer powder is first loaded into the die as it passes beneath the feeder, and then the second layer powder. The tablet is then compressed in one or two phases as a whole.

Limitations of single sided press:

· No individual layer weight control or monitoring.

· There's no obvious visual difference between the two layers.

· Due to the small compression roller, the first layer dwell time was extremely short, which could have led to issues with hardness, capping, and poor de-aeration.

Fig. Single sided tablet machine

Dwell time:

The period of time that the compression force is more than 90% of its maximum value is known as the dwell time. Extended dwell durations play a significant role in the production of high-quality tablets, particularly when compressing challenging formulations.

Fig. Double sided tablet press

Compression force:

For many bilayer formulations to maintain the capacity to connect with the second layer, the first layer compression force must be less than 100 daN. This ability may be lost and there may not be enough bonding between the two layers above 100 daN, which would cause the bilayer tablet to become less rigid and the two layers to separate.

Double sided tablet press:

Compression force is used by the majority of double-sided tablet presses with automated production control to track and regulate tablet weight. The control system measures the effective peak compression force applied to each tablet or layer at the layer's principal compression. When necessary, the control system uses this measured peak compression force as a signal to reject tablets that are out of specification and adjust the die fill depth.

Bilayer tablet press with displacement:

The compression force-based method and the displacement pill weight control principle are essentially unrelated. The applied pre-compression force determines the control system sensitivity when sensing displacement rather than the weight of the tablet.

Fig. Bilayer tablet press with displacement

Ø Maintaining an attractive product identity.

· Must be strong enough to endure mechanical shocks during the manufacturing, packing, transportation, and dispensing processes.

· Must possess the chemical and physical stability necessary to hold onto its physical characteristics throughout time. The drug agents must be able to be released from the bi-layer tablet in a consistent and repeatable way.

· Needs to have a shelf life that is chemically stable to prevent the therapeutic ingredients from changing.

Evaluation of Bilayer Tablets:¹⁴

1. General appearance:

Consumer acceptability of a tablet is largely dependent on its overall design, visual identity, and "elegance." Included are the dimensions, colour, texture, taste, consistency, physical faults, and legibility of any identifying markings on the tablet, as well as its shape, size, and colour.

2. Size and Shape:

It is possible to monitor, regulate, and characterize the tablet's dimensions.

3. Tablet thickness:

When counting with filling equipment and replicating appearance, tablet thickness is a crucial factor. The tablets' consistent thickness is used by some filling machinery as a counting mechanism. A micrometre was used to measure the thickness of ten pills.

4. Weight variation:

Conventional protocols are adhered to, as outlined in the official records.

5. Friability:

The forces that cause tablets to chip, cap, or shatter most frequently are friction and shock. The friability test, which assesses the tablet's resistance to abrasion during handling, packaging, and shipping, is closely associated with tablet hardness. For most measurements, the Roche friabilator is utilized. A number of tablets are weighted and put within the device, where they are subjected to repetitive shocks and rolling while falling six inches every time the device turns. The pills are weighed after four minutes of therapy, or 100 revolutions, and the weight is compared to the starting weight. Tablet friability is measured by the amount of loss from abrasion. A percentage is used to express the value. During the friability test, a weight loss of no more than 1% of the tablets' total weight is deemed generally acceptable, and any shattered or broken tablets no tablets are taken up. Friability values are typically not computed during capping. While thin tablets with a high diameter frequently exhibit extensive capping, thicker tablets may be less likely to do so, suggesting that thicker tablets have less internal tension. The weight loss of the tablet is the indicator of friability and can be expressed as a percentage as follows:

Initial weight (W1) – final weight (W2)

Friability (%) = ----------------------------------- x 100

Initial weight (W1)

6. Hardness:

The hardness of tablets determines their resistance to capping, abrasion, or breaking during handling, transportation, and storage before to use. Monsanto produced and released the compact and lightweight hardness tester in the middle of the 1930s. It is currently known as the Stokes or Monsanto hardness tester. When a coil spring's force is applied to a tablet diametrally, the device calculates the force needed to break it.

Determinations of hardness, or more accurately, crushing strength, are made during the creation of tablets and are used to establish if the tablet machine's pressure has to be adjusted. A tablet that is too hard might not dissolve within the time frame needed to meet the dissolution standards, while a tablet that is too soft might not be able to handle handling during further processing, like coating, packing, and shipping. Kilograms of force are needed to shatter the tablet, and 4 kg is typically thought to be the minimum crushing strength needed to produce good tablets.

Oral pills typically weigh between 4 and 10 kg; however, some sustained release tablets weigh between 10 and 20 kg, whereas hypodermic and chewable tablets often weigh much less (3 kg). Porosity and density are two more tablet qualities that have been linked to tablet hardness. Hardness often rises with regular tablet storage and is influenced by the form, chemical makeup, binding agent, and compression pressure.

7. Stability Study (Temperature dependent)¹⁵

The bilayer tablets are stored for the duration required by the ICH recommendations for expedited research, in appropriate packaging, and under the following conditions.

After 15 days, the tablets were taken out and their physical characteristics (drug content, hardness, friability, and dissolution, among other things) were examined. The kinetics of deterioration are ascertained by fitting the collected data into first order equations. To calculate the shelf life at 25°C, accelerated stability data are shown using the Arrhenius equation.

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15. Indian Pharmacopoeia 1996. The Controller of Publication. Delhi, Vol‐2, p‐735.

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Received on 08.12.2023 Modified on 25.12.2023

Res. J. Pharma. Dosage Forms and Tech.2024; 16(1):47-50.

DOI: 10.52711/0975-4377.2024.00008