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Crystals 2017, 7(5), 131; doi:10.3390/cryst7050131

Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices

1
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
2
Pfizer Inc., Groton, CT 06340, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Hugo K. Christenson
Received: 30 March 2017 / Revised: 2 May 2017 / Accepted: 5 May 2017 / Published: 9 May 2017
(This article belongs to the Special Issue Effects of Confinement and Topography on Crystallization)
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Abstract

While porous silica supports have been previously studied as carriers for nanocrystalline forms of poorly water-soluble active pharmaceutical ingredients (APIs), increasing the loading of API in these matrices is of great importance if these carriers are to be used in drug formulations. A dual-stage mixed-suspension, mixed-product removal (MSMPR) crystallizer was designed in which the poorly soluble API fenofibrate was loaded into the porous matrices of pore sizes 35 nm–300 nm in the first stage, and then fed to a second stage in which the crystals were further grown in the pores. This resulted in high loadings of over 50 wt % while still producing nanocrystals confined to the pores without the formation of bulk-sized crystals on the surface of the porous silica. The principle was extended to another highly insoluble API, griseofulvin, to improve its loading in porous silica in a benchtop procedure. This work demonstrates a multi-step crystallization principle API in porous silica matrices with loadings high enough to produce final dosage forms of these poorly water-soluble APIs. View Full-Text
Keywords: MSMPR; nanocrystals; confined crystallization MSMPR; nanocrystals; confined crystallization
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dwyer, L.; Kulkarni, S.; Ruelas, L.; Myerson, A. Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices. Crystals 2017, 7, 131.

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