(645f) Application of Materials Science Approaches to Facilitate Drug Substance and Product Processing

Application of
Materials Science Approaches to Facilitate Drug Substance and Product
Processing

Raimundo Ho and
Thomas B Borchardt

Abbott Laboratories,
Global Pharmaceutical R&D

An important aspect of the
development of drug substance manufacturing processes is the identification of
the properties critical to formulation processing.  Historically, the emphasis
has been on particle size with less attention to other physical properties such
as particle shape and surface properties.  The emergence of new
characterization technologies in the pharmaceutical industry has broadened the
scope of properties that can be evaluated, but simultaneously expands the
amount of data available for interpretation.  From a practical point of view,
modeling approaches that facilitate a quick determination of the key attributes
that impact the processing behavior of the drug substance can drive efficiency
in property characterization.  A chemometric approach has been developed to identify
critical physical property parameters impacting flow function coefficients (FFCs)
of bulk powders. A partial least squares (PLS) model was established to
correlate metrices of particle physical property characteristics with powder FFCs,
with the aim of maximizing model predictability (Q²) whilst
minimizing the number of latent factors and root mean square error of the
response.  The model indicates that bulk powder flow is not only affected by particle
size distribution, but may also be significantly affected by the shape distribution,
span of the distribution, and surface energetics. An understanding of the
fundamental physical property characteristics will drive efficiency in
characterization and aid the design of isolation processes to target particle
attributes for downstream formulation and processing needs.