465879 Silica Nanoparticle-Seeded Microfluidic Emulsion Crystalisation - Crystalline Drug Composite Microparticles

Friday, November 18, 2016: 2:30 PM
Continental 5 (Hilton San Francisco Union Square)
Saif A. Khan1, Denise Zi Ling Ng2 and Eunice Wan Qi Yeap2, (1)Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, Singapore, (2)Chemical and Biomolecular Engineering, National University of Singapore, SINGAPORE, Singapore

We have recently demonstrated the fabrication of co-formulated drug-(polymeric) excipient microparticles with exquisite control over particle size, shape and polymorphism, using microfluidic emulsion crystallization and model hydrophobic drugs such as ROY and Carbamazepine [1]. In some cases, the co-formulation of polymeric excipients and drugs, depending on their mutual interactions, may lead to problems of drug-polymer miscibility and result in amorphous solid dispersions. [2-3] These amorphous solid dispersions may present storage problems, as they can crystallize over time. Here, we demonstrate the use of colloidal silica particles as excipients in microfluidic emulsion crystallization of a model hydrophilic drug. Silica nanoparticles, conventionally incorporated in solid dosage forms at the later stages of formulation, function as glidants or fillers. In contrast, in our work, the silica particles act as heterogeneous seeds for nucleation of the drug, thereby drastically reducing crystallization times, while also acting as an excipient that improve flowability and enable excellent crystallinity. Another notable advantage of using colloidal silica is its general applicability to a wide range of drugs, since the silica particles can easily be functionalized [4]. We envision significant potential for drug-silica composites prepared by microfluidic emulsion crystallisation, which allow rapid crystallization of a variety of drugs and their direct formulation into spherical microparticles without compromising the crystallinity of the drug product.

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CONTACT * S. A. Khan, Tel: +65-6516-5133; saifkhan@nus.edu.sg

[1] Leon, R. A. L.; Badruddoza, A. Z. M.; Zheng, L.; Yeap, E. W. Q.; Toldy, A. I.; Wong, K. Y.; Hatton, T. A.; Khan, S. A., Highly Selective, Kinetically Driven Polymorphic Selection in Microfluidic Emulsion-Based Crystallization and Formulation. Crystal Growth & Design 2015, 15(1), 212-218.

[2]Huang, Y.; Dai, W. G., Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B 2014, 4(1), 18-25.

[3] Marsac, P. J.; Shamblin, S. L.; Taylor, L. S., Theoretical and practical approaches for prediction of drug-polymer miscibility and solubility. Pharm Res 2006, 23(10), 2417-26.

[4] Md. Badruddoza, A. Z.; Toldy, A. I.; Hatton, T. A.; Khan, S. A., Functionalized Silica Nanoparticles as Additives for Polymorphic Control in Emulsion-Based Crystallization of Glycine. Crystal Growth & Design 2013, 13 (6), 2455-2461.

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