Evaluating mechanical properties and tabletability of pharmaceutical powders with a novel gravitation-based high-velocity compaction method

Developing new pharmaceuticals is costly and time-consuming. New methods are always in demand for various stages of product development. Investing in the early phases of development can save a significant amount of resources in the long term.
Tablet is still the most commonly used pharmaceutical dosage form. Tablets are often produced by powder compression. Powder particles fragment and deform under pressure, allowing new bonds to form between them. Modern machines can produce over one million tablets per hour.
The mechanical properties of the powders have a remarkable impact on compact formation. For example, excessive elasticity in a powder mixture can lead to weak or defected tablets being produced. Therefore, the mechanical properties need to be studied. Devices known as tableting simulators have been designed to aid in developing adequate tablet formulations. These machines are useful, but they can still be quite expensive and large. The results obtained by these machines are not always universally applicable, and further interpretation is often required.
In this thesis, a novel gravitation-based high-velocity compaction (G-HVC) method was developed to study the compressibility and tabletability of powders in a cost-efficient and straightforward manner. The method is based on a freely falling steel bar, which compresses the powder sample inside a custom-made die. The movement of the bar and the deformation wave of the system base were monitored by high-accuracy displacement sensors. Displacement graphs could then be derived further. All data obtained by the method was ultimately only based on the displacement data.
First, microcrystalline cellulose (MCC) and starch samples were compressed to demonstrate the functionality of the method. MCC was shown to be more compressible and less elastic than starch. Apparent differences in the relative volume decrease and the compression behaviour of these two materials could be seen.
Next, various materials were studied more comprehensively. Two different setups with varying pressure were in use. Lactose grades and glucose showed effective fragmentation and reached true density with both setups. MCC grades were clearly pressure-dependent and showed slower gradual deformation, indicating plastic behaviour. Compression pressure was not high enough to effectively fragment calcium phosphate. Starch showed most elasticity of all the samples. In summary, all examined materials could be successfully categorized in terms of their mechanical properties.
Finally, the practical relevance of the method was shown by creating a model between the compaction energy values determined by G-HVC method and the tensile strength of tablets produced with a tableting machine. Three different formulations consisting of MCC, calcium phosphate, theophylline and HPMC were granulated utilizing a fluid bed system. There was a good correlation between compaction energy and tensile strength.
In summary, the G-HVC method was proven to be a reliable and cost-efficient tool in the examination of the mechanical properties of powders. The method was also capable of producing practically relevant results. The method fits well in modern pharmaceutical research where material-sparing, straightforward and reliable methods are in demand.

Download the full Disseration here: Evaluating mechanical properties and tabletability of pharmaceutical powders with a novel gravitation-based high-velocity compaction method

by Timo Tanner – Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy, University of Helsinki, Finland

Materials
A total of 12 different materials was studied, including Amioca powder TF (National Starch), anhydrous calcium hydrogen phosphate (Merck), anhydrous glucose Ph. Eur. (Yliopiston Apteekki), Avicel PH-102 (FMC BioPolymer), Avicel PH-200 (FMC BioPolymer), dicalcium phosphate dihydrate (DCP) (Chemische Fabrik Budenheim), Methocel (DOW Chemical Company), Pharmatose 80M (DMV-Fonterra Excipients), Pharmatose 200M (DMV International), Starch 1500 (Colorcon), theophylline Ph.Eur./USP (BASF) and Vivapur 101 (JRS Pharma). Magnesium stearate Ph. Eur. (Yliopiston Apteekki) was used as a lubricant in some formulations and it was also mixed with technical grade acetone producing 5 w/w (%) mixture to lubricate the device. Amioca powder is a type of starch, Avicel and Vivapur are different grades of MCC, Pharmatose is lactose monohydrate and Methocel is hydroxypropyl methylcellulose (HPMC). Materials were selected to present a wide range in terms of mechanical properties.