Abstract
The quality by design (QbD) initiative is promoting a better understanding of excipient performance and the identification of critical material attributes (CMAs). Despite microcrystalline cellulose (MCC) being one of the most popular direct compression binders, only a few studies attempted identifying its CMAs. These studies were based either on a limited number of samples or on MCC produced on a small scale and/or in conditions that deviate from those normally encountered in production. The present work utilizes multivariate analyses first to describe a large database of MCCs produced on a commercial scale, including an overview of their physicochemical properties, and secondly to correlate the most significant material attributes with tabletability. Particle size and moisture content are often considered as the most common if not the sole CMAs with regard to MCC performance in direct compression. The evaluation of more than 80 neat MCCs and the performance of selected samples in a model formulation revealed the importance of other potential critical attributes such as tapped density. Drug product developers and excipient suppliers should work together to identify these CMAs, which may not always be captured by the certificate of analysis.
Full article: http://authors.elsevier.com/a/1R3nm1M49k6YWf
Gregory Thoorens(a), Fabrice Krier(a), Eric Rozet(b), Brian Carlin(c), Brigitte Evrard(a)
(a) Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium
(b) Laboratory of Analytical Chemistry, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium
(c) FMC Health and Nutrition, Ewing, NJ, USA
Received 3 April 2015, Revised 7 May 2015, Accepted 9 May 2015, Available online 14 May 2015