A BETTER WAY TO MAKE BILAYER TABLETS

Q&A 1 > Bilayer Tablets – Q&A

Questions & Answers

© GEA Process Engineering nv 2021

Q1 What is the principle for 1st layer sampling? How does it work? Is it possible to do intermittent sampling of first layer online? Or do we need to stop the machine to collect each sample of the 1st layer?

A1 The first layer can be sampled while the press is running. When a sample is requested, the first layer compression height is automatically reduced to increase the hardness of the first layer tablet and enable ejection of a sufficiently strong tablet.

Q2 If both layers use the same colour, is there a method to check if any later mixing is present?

A2 When both layers have the same color, there is no easy way to evaluate the cross contamination. Analytical methods need to be applied to evaluate the presence of second layer material in the sampled first layer tablets.

Q3 What are the various factors for layer separation? A3 The tendency of two layers to separate depends highly on the formulation.

Particles of both layers need to be capable of bonding to each other. Often a relatively low first layer compression force needs to be applied to make sure that the two layers can still interact with each other.

Q4 Do materials in layer 1 and layer 2 need similar partical size distribution/densities? A4 No, the particle size distribution or density does not need to be the similar. For the

second layer, there is no suction fill and the maximum fill depth is limited, so the density and flowability of the material may have to be tuned to allow for stable and uniform die filling. The first and second layer also need to be able to bond to each other.

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Q&AQ 5

Is there any rule for selecting layer weight ratio for bi-layer tablets? If not, what is the best way to decide the ratio?

A5 There are multiple factors that determine the applicable layer thicknesses and weight ratios: - The minimum applicable quantity for the first layer is mainly determined by its

volume during first layer compression. If the volume is too small, the punch tips may already collide before the desired compression density is reached. This is less of a limitation for the second layer material because the total quantity of material in the compressed state will always exceed the sum of the cup volumes, so a small second layer will always be compressed.

- The minimum applicable quantity for the second layer will mainly be determined by the size of the tablet (the second layer should at least cover the entire tablet surface) and required accuracy of second layer weight control. The smaller the layer, the more difficult is becomes to measure small differences in weight and the more small variations in first layer properties will affect the measurements.

- The larger the second layer, the more easy it becomes to control the individual layer weight. The attainable weight for the second layer may however be limited by the reduced overfill and fill capacity (determined by the top punch penetration of first layer compression) and the absence of suction fill.

Q6 Tablet thickness is not constant, correct? A6 Indeed. In case of roller displacement, the thickness will slightly differ with

weight. For first layer, roller displacement is only applied at pre-compression. The main compression of the first layer is with constant thickness (fixed rollers) to make sure the fill of the second layer is equal for each tablet.

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Q7 Is it possible to take a sample from both layers seperately? A7 Samples can be taken from the first layer and total tablet.

The second layer cannot be sampled separately.

Q8 What is the main objective of having a main compression stage for the 1st layer? A8 At pre-compression, the first layer tablet weight is determined by applying a constant

force and measuring the tablet height. As the thickness slightly differs with weight, a main compression step is used to compress the tablets to constant thickness. A fixed first layer thickness will ensure that the fill depth for the second layer is equal for each tablet.

Q9 What is the roller capacity for both pre & main rollers? A9 The maximum compression force at pre-compression is 10 kN. At

main compression, a force of up to 100 kN can be applied.

Q10 What is the scrapping facility for both layers after the feeder? Is the powder collected or is it suctioned after scrapping from the turret? If the 2nd feeder is closed then where is the scrapping powder collected?

A10 The material of one layer can be recuperated by using an open feeder with recuperation using a central groove in the die table. A closed feeder is used for the other layer and he material scraped off after that feeder is directed to the outside of the turret and removed by means of a dust extraction system.

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Q&AQ 11

How do you ensure the two layers don't get mixed up?

A11 Several scrapers and extraction points are provided to keep the die table clean and prevent cross-contamination of both layers.

Q12 If the tablet weight is 1700 mg then what would be the maximum production per hour?

A12 The maximum attainable production speed will highly depend on the material properties, ratio between the layers, compression characteristics, yield requirements etc. GEA advises to take trials on the Performa D in its trial center in Belgium in order to determine the machine settings to get to the right tablet quality (weight, hardness, cross contamination, adhesion,… ) and targeted output.

Q13 Is the displacement of the piston above pre & main compression measured? A13 Yes, the displacement of the piston at pre- and main compression is accurately

measured using a displacement sensor connected to the roller yoke.

Q14 Is vacuum suction required for better control? A14 Vacuum suction at several points in the process is important to prevent cross-contamination Continued

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GEA Pharma & Healthcare For further information please contact

Valentin Davila Sales Manager for Tablet Compression E: valentin.davila@gea.com T: +32 2 363 8371

gea.com/contact

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Q15 Can we fix the force in range? A15 The main compression force and thus hardness of the final

bilayer tablet can be controlled in two ways:

- Either the aircompensator is activated (roller displacement is allowed) due to which each individual tablet will see the same force applied to it.

- Or the final tablet is compressed to equal thickness. In such case the applied force is measured and when going out of the control limits, the tablet thickness will automatically be slightly adjusted to bring the force back to the target value. When the force goes out of the set reject limits, the tablet will get rejected. In this way the control system is capable of keeping the average force constant.

Q16 Does height control refer to the thickness of tablet? A16 Yes, if a constant force is applied to the tablet, the density remains about

the same and any variation in weight will result in a variation in volume or thickness, which will be measured by measuring the roller displacement

Q17 Is the lifespan of punches altered by increased dwell time? A17 The impact of the punch onto the roller is slightly higher when applying

roller displacement, especially when applied at the final compression station where forces are high, so the wear may be somewhat higher

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