Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices
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...
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| Format: | Article |
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MDPI AG
2017
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| Online Access: | http://hdl.handle.net/1721.1/112090 https://orcid.org/0000-0002-7596-3595 https://orcid.org/0000-0002-5054-9080 https://orcid.org/0000-0002-7468-8093 |
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| author | Dwyer, Leia Mary Kulkarni, Samir Ruelas, Luzdary T. Myerson, Allan S. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Dwyer, Leia Mary Kulkarni, Samir Ruelas, Luzdary T. Myerson, Allan S. |
| author_sort | Dwyer, Leia Mary |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T07:56:27Z |
| format | Article |
| id | mit-1721.1/112090 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T07:56:27Z |
| publishDate | 2017 |
| publisher | MDPI AG |
| record_format | dspace |
| spelling | mit-1721.1/1120902022-09-30T01:10:37Z Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices Dwyer, Leia Mary Kulkarni, Samir Ruelas, Luzdary T. Myerson, Allan S. Massachusetts Institute of Technology. Department of Chemical Engineering Dwyer, Leia Mary Kulkarni, Samir Ruelas, Luzdary T. Myerson, Allan S. 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. 2017-10-31T14:17:32Z 2017-10-31T14:17:32Z 2017-05 2017-05 2017-10-20T19:56:45Z Article http://purl.org/eprint/type/JournalArticle 2073-4352 http://hdl.handle.net/1721.1/112090 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 https://orcid.org/0000-0002-7596-3595 https://orcid.org/0000-0002-5054-9080 https://orcid.org/0000-0002-7468-8093 http://dx.doi.org/10.3390/cryst7050131 Crystals Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG MDPI |
| spellingShingle | Dwyer, Leia Mary Kulkarni, Samir Ruelas, Luzdary T. Myerson, Allan S. Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices |
| title | Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices |
| title_full | Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices |
| title_fullStr | Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices |
| title_full_unstemmed | Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices |
| title_short | Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices |
| title_sort | two stage crystallizer design for high loading of poorly water soluble pharmaceuticals in porous silica matrices |
| url | http://hdl.handle.net/1721.1/112090 https://orcid.org/0000-0002-7596-3595 https://orcid.org/0000-0002-5054-9080 https://orcid.org/0000-0002-7468-8093 |
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