Meeting the Standards of Tomorrow's Pharmaceutical Production

1. Poorly Flowing Nutraceutical roduct Requiring High Compression Forces

The study was carried out on a customer formulation based on Berberisaristata extract and vitamin B1 and B6. The mean particle size distribution of the blend is around 41.37 micron, with bulk and tapped density of respectively 0.39 and 0.56 g/cm3. The powder, as results from the Carr Index value of 30, has a poor flowability.

Target of the study:

Obtain oblong shape tablets of 20.5 mm x 9.5 mm with an average weight of 1,100 mg with percent deviation related to the average less than 10 per cent and hardness within 140–160 N range (customer requirements).

Process parameters:

Process description:

The product has an extremely low mean particle size and low bulk density. Already at low speeds, the requested main compression force approaches 85–90 kN, and also in pre compression it is necessary to apply almost 60 kN. This is an example of a poorly compactable product that requires very high force to be applied in both the main compression and in pre-compression in order to form solid bridges between the particles. The production speed of 61,560 tablets/hour on Prexima 300 tablet press is equal to 22 ms of dwell time, with Euro D punches. Owing to the product’s intrinsic characteristics, lower dwell time is deleterious from the point of view of product hardness: the force has to be applied for a determined extent of time, in this case not less than 22–25 ms.

The higher mass uniformity was achieved by using the round profile paddles with reversed rotation (outward counter-rotating): the round profile is useful when it is necessary to avoid powder compaction (in this case the powder is cohesive and tends to compact), whereas the reversed sense of paddle rotation helps to fill the dies better. In fact the left paddle moves in the opposite direction with respect to the turret and this may be helpful in some cases. Despite the product’s level of difficulty, the tablets obtained were compliant with the customer requirements.

2. Antibiotic Based Formulation With Highly Elastic Properties Under Compression

The study was carried out on a formulation based on amoxicillin trihydrate. The composition is shown in the table below.

The mean particle size distribution of the blend is around 650 micron, with bulk and tapped density of respectively 0.63 and 0.75 g/cm3.The powder, as results from the Carr Index value of 23, has a good flowability.

Target of the study:

Obtain oblong shape tablets of 17 mm x 7 mm with average weight of 600 mg (API content circa 525 mg) with percent deviation related to the average less than 5 per cent. Parameters such as hardness uniformity, friability and disaggregation time were evaluated as well.

Process parameters:

Process description:

The amoxicillin exhibits highly elastic properties that cause variations in the hardness value of single tablets. The same diameter of the pre-compression and of the main compression roller enables to transform the tableting process in two identical compression steps, rather than discriminating between the pre-compression and main compression steps.

In this case, the pre-compression force was kept at 15 kN, whereas the main compression was slightly higher, between 18 and 20 kN. This seems to improve the hardness uniformity, as can be seen from the table below. All the other parameters comply with the requirements of the European Pharmacopoeia: