Designing for Compaction in Tablets with Spray Dried Intermediates

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)