Facilitating Drug Product Development using Indentation Experiments on an Atomic Force Microscope

R. Wadams
Pfizer Inc.,
United States

Keywords: characterization, drug development


The pharmaceutical industry is experiencing an increasing necessity for materials characterization platforms that revolutionize the industry’s capabilities to expedite and enhance drug development. With an upward trend in preclinical development costs, regulatory agencies implementing avenues for expedited development, as well as the proliferation of nanotechnology in drug products, there is a need for techniques which can both characterize materials on the nanometer scale, and provide support for an increasingly efficient drug development paradigm1,2,3. Atomic force microscopy is among the techniques that are gaining popularity for their effectiveness in facilitating the characterization of pharmaceutical materials at the nanoscale, while providing opportunities to support expedited drug development models. Atomic force microscopy (AFM), along with its related spectroscopic techniques, is arguably unprecedented in its ability to provide a series of characterization tools within one technological platform, where a material’s physical and chemical properties may be simultaneously measured and correlated to topography. One characterization scheme within AFM’s repertoire, which is gaining utility in the pharmaceutical industry, is the assessment of a material’s mechanical properties through nanoindentation, or force modulated imaging4,5. Since an organic material’s mechanical response to stress is dictated by its molecular composition, atomic interactions, and molecular packing geometry, one may discriminate different materials through a mechanical property measurement; within this characterization scheme, one can therefore potentially assess a material’s chemical and physical stability, as well as providing insight into how a material may withstand the stresses imposed by manufacturing4,5. This presentation will review recent advances in supporting drug product development with AFM-mediated nanoindentation and force modulated imaging. Additionally, our developments in using nanoindentation to measure the mechanical properties of organic single crystals, and its relevance to solid form selection will be discussed. [1] Mullin, Rick. “Tufts Study Finds Big Rise In Cost of Drug Development.” American Chemical Society, 20 November 2014. Web. 15 February 2016. http://cen.acs.org.proxy1.athensams.net/articles/92/web/2014/11/Tufts-Study-Finds-Big-Rise.html [2] U.S. Food and Drug Administration. “White Paper: FDA and Accelerating the Development of the New Pharmaceutical Therapies.” U.S. Food and Drug Administration, 23 March 2015. Web. 15 February 2015. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm439082.htm [3] E.S. Kawasaki, A. Player. Nanomedicine: Nanotechnology, Biology, and Medicine 1. 2005, pp. 101-109. [4] S. Varughese, M.S.R.N. Kiran, U. Ramamurty, and G.R. Desiraju, Angew. Chem. Int. Ed. 2013, 52, 2701-2712. [5] X. Cao, M. Morganti, B.C. Hancock, and V.M. Masterson, J. Pharm. Sci., 2010, 10, 4307-4316.