Saif A. Khan, Department of Chemical and Biomolecular Engineering
National University of Singapore, Singapore

This paper will present an overview of recent progress towards single-step fabrication of pharmaceutical drug-excipient microparticles through microfluidic emulsion-based processing. In the pharmaceutical industry, active pharmaceutical ingredients typically undergo a series of secondary manufacturing operations, such as crystallization and formulation with additives and excipients, to obtain drug products of varying types, such as orally ingestible tablets or injectables. Traditionally, drug substances crystallized in batch vessels allow poor and coarse control over crucial crystal attributes, which tremendously impacts the number of subsequent processing steps required to arrive at the final drug product. We have recently developed microfluidics-based methods which allow for crystallization and formulation of drug substances to be carried out in a single processing step, leading to monodisperse spherical granules with unprecedented control over crystal attributes such as shape, size and polymorphism [1-2]. These methods couple the usage of microfluidics for emulsion generation and evaporative or anti-solvent crystallization where, by tuning the various process parameters (such as droplet sizes and compositions, solvent removal rates, etc.), we are able to crystallize and formulate a wide range of hydrophilic and hydrophobic model and commercial drugs into monodisperse spherical microparticles with tunable properties. The versatility of emulsion-based processing for formulating drug-excipient composite particles with tunable structures will be showcased in this paper with different drug-excipient systems. Specifically, we will discuss how an interplay of phase separation, drug crystallisation and polymer vitrification in drug and polymer-containing droplets during evaporative or anti-solvent crystallisation leads to a diversity of microparticle structures which exhibit different drug release profiles [3]. We will also discuss the fabrication of
 composite microparticles containing drug and colloidal excipients with exquisitely tunable crystalline microstructure by co-confinement
of a drug and a colloidal excipient dispersion within sub-millimeter droplets [4]. These engineered particles embody the idea of drug product intermediates that lie at the drug substance-drug product interface. In conclusion, microfluidic emulsion-based crystallisation enables novel routes for drug particle engineering, and challenges the conventions of secondary pharmaceutical manufacturing.

Key Words: Particle Engineering, Microfluidics, Drug-excipient Composites.


  1. Yeap, E. W. Q., Acevedo, A. and Khan, S. A., Organic Process Research and Development, 23(3), 375-381 (2019).
  2. Yeap, E. W. Q., Ng, D. N. Z., Lai, D., Sharpe, S., Ertl, D. and Khan, S. A., Organic Process Research and Development, 23(1), 93-101 (2019).
  3. Yeap, E. W. Q., Ng, D. Z. L., Ammu, P., Somasundar, A., Acevedo, A. J., Xu, Q., Salahioglu, F., Garland, M. V. and Khan, S. A., Crystal Growth and Design, 17(6), 3030–3039 (2017).
  4. Yeap, E. W. Q., Ng, D. N. Z., Lai, D., Sharpe, S., Ertl, D. and Khan, S. A., Crystal Growth & Design, 18(10), 5727-5732 (2018).