(661g) Designing for Compaction in Tablets with Spray Dried Intermediates

Authors: 
Ploeger, K., Merck & Co, Inc.
Temtem, M., Hovione FarmaCiência SA
Cordeiro, P., Hovione

Title:  Designing for Compaction in Tablets with
Spray Dried Intermediates

Authors:  Kristin Ploeger (kristin.ploeger@merck.com),
Marcio Temtem (mtemtem@hovione.com), Paula Cordeiro (pcordeiro@hovione.com), Angela
Aghajanian (angela.deese@merck.com)

Abstract:

In an environment with increasing numbers of poorly-soluble
drug substances, spray drying is used to enhance the solubilization of some of
these molecules.  Inclusion of this unit operation in the manufacture of oral
solid dosage forms results in a new challenge, where the compactability for the
formulation is frequently impacted in three separate unit operations (spray
drying, roller compaction, and tabletting).  The interconnection between the
unit operations requires a Quality by Design approach to development, where impact
of process parameters across multiple unit operations is considered since the
design space in one unit operation has the potential to restrict the design
space in the others. 

Approaches for designing the spray dried particle attributes
will be discussed. The combination of modeling and simulation
tools with process understanding and prior knowledge were crucial to deliver a
commercially viable process. Moreover, the description of the process and its
design space through meaningful and scale-independent parameters (some of them,
such as relative saturation of the drying gas and mean droplet size, accurately
estimated by modeling tools) were used in the benefit of the scale-up (Figure
1).  Corrections between process parameters and material attributes will be
presented.

Figure 1 ? Schematic
representation of the lab and commercial thermodynamic design space

Spray dried particle attributes
were evaluated to determine which, if any, could be a surrogate measure of
particle compactability.   A multivariate study of compactability across
the three unit operations was performed (Figure 2), to evaluate if enhancement
of compactability in the spray dried particles could permit more aggressive
roller compaction conditions, without impact to the tabletting process or final
attributes (such as disintegration, dissolution, and friability).   While traditional
studies of roller compaction typically include independent variables like roll
pressure, this work will discuss the potential benefits (and challenges) of
designing the DoE with a parameter like tensile strength (analogous to the
practice of designing tabletting DoEs with tablet hardness as a parameter).

Figure 2 ? Schematic of the proposed experimental protocol
(Images ? Hovione copyright)