Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices
Author(s)Dwyer, Leia Mary; Kulkarni, Samir; Ruelas, Luzdary T.; Myerson, Allan S.
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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.
DepartmentMassachusetts Institute of Technology. Department of Chemical Engineering
Dwyer, Leia et al. “Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices.” Crystals 7, 5 (May 2017): 131 © 2017 The Authors
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