(778a) Formulation Strategies for Solid Dispersions Containing Tablets

Formulation strategies for solid dispersions
containing tablets

S.
Doktorovova, E. Voney, J. Henriques

R&D Drug Product Development, Hovione Farmaciência S.A,
Sete Casas, 2674-506 Loures, Portugal

In this work we
present the development of formulation strategies for amorphous solid
dispersions containing hypromellose acetate-succinate (HPMC-AS-M). Solid
dispersions, especially spray dried, frequently have poor tableting properties
due to low bulk densities and small particle size [1]. Tablet formulation then
relies on excipients with capacity to improve compactability and blend flow.
Three strategies are outlined: i) using a plastic filler/binder that greatly improves
blend compactability and assure good mechanical strength of the tablets, ii)
using a free flowing filler to improve powder flow properties and guarantee low
mass and content variation iii) use a combination of a plastic and brittle
excipient. The later should assure a good balance between acceptable powder
flow and compactability. For the purpose of this work, a simple formulation
compromising the solid dispersion (here represented by sieved HPMC-AS-M), a
diluent or combination of two diluents, a disintegrant and a lubricant was
considered.

The strategy
based on formulating HPMC-AS-M with free flowing diluent largely improved
powder flow properties of the blend without compromising compactability, but
the improvement of powder flow properties did not translate into good tableting
properties. Formulation of HPMC-AS-M with plastic diluent/binder resulted in
excellent mechanical strength of the produced tablets but increasing ratio of
the diluent compromised mass uniformity. A combination of a plastic and a well
flowing diluent was therefore required to achieve a compromise between
mechanical strength and mass variability. Fine tuning of the required ratio of
diluents depended on the percentage of polymer present in the blend, tablet tensile
strength being impacted to greater extent by increased polymer fraction than
mass variability.

A model using
bulk properties of excipients and polymer was set up as a tool to optimize the
formulation powder flow properties of blends and quality attributes of tablets.
Various mixture models were used for each property, the one that showed the
best correlation between predicted and observed values were selected for the
model. Prediction of blend powder flow and tablet properties using the model
will enable sparing material in solid dispersion tablet development.

Figure 1:
Modeling of a) powder flow properties using specific energy (SE, mJ/g) and c) tableting
properties using tablet tensile strenght (TS, MPa) at 12 kN compression
force and b) a sweet spot between acceptable powder flow and tableting
properties.

References

[1] Henriques, J., Valente, P. & Winters, C. “Formulating
Amorphous Solid Dispersions: Bridging Particle Engineering and Formulation”,
American Pharmaceutical Review, Nov/Dec. 2016.