(703h) Linking Moisture Induced Variations in Pharmaceutical Primary Powders to Their Tableting Performance

A drug is only a small
proportion of a pharmaceutical tablet. Other excipients, for example binders
and disintegrants, make up the bulk volume of the
dosage form and therefore the properties they possess are important in
determining the final quality and compaction attributes of a tablet.
Pharmaceutical formulations are often wet granulated, for example via twin
screw granulation (TSG), prior to compaction to ensure homogeneity and to
improve their flowability. The tableting properties of pharmaceutical
formulations can be characterised by their compressibility and compactibility. Compaction consists of compression and
consolidation of a particulate-gas system due to an applied force and such
mechanisms have become an important part of pharmaceutical development.

We have observed that tablet
tensile strength varies depending on the relative humidity (RH) upon storage of
compressed tablets or granules produced via TSG. This work has led to further
investigation of pharmaceutical primary powders and how tablet properties
change with moisture content. The aim of the current work is to investigate the
influence of material properties, for example moisture content and solubility
on final tablet attributes. Ungranulated powders of varying solubility,
hygroscopicity and molecular weight were chosen for testing purposes. Powders
were equilibrated at differing relative humidity levels before using
characterisation techniques to determine tablet compactibility,
porosity, and tensile strength. Tabletability
describes the strength a tablet possesses after compaction under a given
pressure. The tabletability profiles in Figure 1 show
tablet strength as a function of compaction pressure for MCC and starch.

Figure 1. Tabletability
profiles for MCC and starch.

Due to the hygroscopic
nature of microcrystalline cellulose (MCC) and starch each powder increases in
moisture content upon storage at increasing relative humidity. Tablet strength
increases with increasing compaction pressure in all cases. A loss in tabletability is seen with the highest moisture content
(6.16%) at compaction pressures over 180 MPa for MCC,
below this compaction pressure the higher moisture content produces the
strongest tablets. Where water aids compaction at low compression, it hinders
tableting at high compaction pressure. A tabletability
profile for lactose (Pharmatose 200M) shows no
significant change in moisture content or tablet strength across the range of
relative humidity the powders are stored at.

Figure 2. Compressibility
profiles for MCC, starch and lactose.

Compressibility describes
how the porosity of a powder changes under pressure and is shown for each
material in Figure 2. With increasing pressure, the tablet density increases,
and tablet porosity approaches zero. MCC is the most plastic material, followed by lactose and finally starch [2]. Porosity approaches zero faster the more plastic a powder is because they
eliminate pores via plastic deformation more effectively. The increasing
moisture content in MCC and starch also plasticizes the material further,
leading to a faster reduction in porosity with increasing moisture content.

By selecting a range of
powders with differing properties it is hoped a link can be made between
structure, moisture content and tablet tensile strength that can be applied
across multiple materials in the future, along with valuable information that
can be applied to optimise the TSG process.

References

[1] C. C. Sun. Mechanism of
moisture induced variations in true density and compaction properties of
microcrystalline cellulose, International Journal of Pharmaceutics, 346 (2008)
93-101.

[3]
D. H. Choi et. al. Material properties and compressibility using Heckel and Kawakita equation with
commonly used pharmaceutical excipients. Journal pd
Pharmaceutical Investigation, 40(4) (2010) 237-244.