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.