Session 3: Particle Engineering and DS-DP Co-Processing Archives - Pharma Crystallization Summit

Particle Surface Engineering for Predictive Enhancement of API Properties

wpadm — Tue, 16 Jun 2020 15:43:37 +0000

Rajesh Dave, New Jersey Center for Engineered Particulates, New Jersey Institute of Technology Newark, NJ, USA dave@njit.edu Particle surface engineering is a cost-effective, promising route to achieve enhancements in the flowability, bulk density and other properties of a variety of cohesive active pharmaceutical ingredients (APIs). This presentation will discuss predictive enhancements after dry coating based particle surface engineering and discuss models and guidelines for the selection of flow aid type and amount, as well as predicting powder bulk properties from their particle-scale properties such as the particle size and distribution, materials density, surface energy, and surface roughness. The use of dry coating in developing direct compression ready blends will be also presented. through dry coating of either API or excipients. Towards those goals, industrially relevant and scalable dry coating devices are used and compared against a material sparing benchmarking device. Mechanistic particle contact models are employed for examining the causes of cohesion reduction and subsequent property enhancements. The bulk property based 2-D processability maps are introduced and used to assess the extent of enhancements in flow and packing as well as the possibility of avoiding wet and/or dry granulation, as well as for moving towards direct compression at high drug loadings. Results are presented to demonstrat that dry coating for particle surface engineering is a powerful technique. Along with our predictive, model-based approach, it can help mitigate problems posed by fine powders, with positive outcomes in flow, and bulk density improvements. Such enhancements enable high drug loaded fine and cohesive API blends through particle engineering. Overall, the bulk property based 2-D processability maps along with dry coating based property enhancements can help make manufacturing decisions regarding the formulation strategy for solid pharmaceutical dosages, presenting a promising platform for commercial applications and cost reduction. Key Words: Cohesive powders, dry coating, flowability, bulk density, predictive models

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Co-processing: An Effective Particle Engineering Approach for Drug Substances

wpadm — Mon, 15 Jun 2020 15:44:44 +0000

Dr. Deniz Erdemir, Principal Scientist Bristol Myers Squibb, New Brunswick/New Jersey Abstract coming soon

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Drug Particle Engineering Using Microfluidic Emulsion-based Crystallization

wpadm — Sun, 14 Jun 2020 15:19:04 +0000

Saif A. Khan, Department of Chemical and Biomolecular Engineering National University of Singapore, Singapore saifkhan@nus.edu.sg 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. References:

Yeap, E. W. Q., Acevedo, A. and Khan, S. A., Organic Process Research and Development, 23(3), 375-381 (2019).
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).
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).
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).

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