Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading
Efficient control of crystallization and crystal properties still represents a bottleneck in the manufacturing of crystalline materials ranging from pigments to semiconductor particles. In the case of pharmaceutical drug manufacture, current methods for controlling critical crystal properties such a...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/123820 |
| _version_ | 1811097296048226304 |
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| author | Eral, Huseyin Burak O'Mahony, Marcus Shaw, Robert M Trout, Bernhardt L. Myerson, Allan S. Doyle, Patrick S |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Eral, Huseyin Burak O'Mahony, Marcus Shaw, Robert M Trout, Bernhardt L. Myerson, Allan S. Doyle, Patrick S |
| author_sort | Eral, Huseyin Burak |
| collection | MIT |
| description | Efficient control of crystallization and crystal properties still represents a bottleneck in the manufacturing of crystalline materials ranging from pigments to semiconductor particles. In the case of pharmaceutical drug manufacture, current methods for controlling critical crystal properties such as size and morphology that dictates the product’s efficacy are inefficient and often lead to the generation of undesirable solid states such as metastable polymorphs or amorphous forms. In this work, we propose an approach for producing crystals of a poorly water-soluble pharmaceutical compound embedded in a polymer matrix. Taking advantage of the composite hydrogel structure, we control the crystallization of the active pharmaceutical ingredient (API), within the composite hydrogel, generating crystalline API of controlled crystal size and loading. The composite hydrogels initially consist of organic phase droplets, acting as crystallization reactors, embedded in an elastic hydrogel matrix. By controlled evaporation of this composite material, crystals of controlled size (330 nm to 420 μm) and loading (up to 85%w/w) are produced. Through the interplay of elasticity and confinement, composite hydrogels control the crystal size and morphology via a two-step mechanism. First, the elastic matrix counteracts evaporation-induced coalescence of the emulsion droplets, keeping droplets isolated. Second, a confinement-induced elastic energy barrier, limits the growth of crystals beyond the size designated by the droplets. The proposed approach can be applied to production of a wide range of crystalline materials. |
| first_indexed | 2024-09-23T16:57:22Z |
| format | Article |
| id | mit-1721.1/123820 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:57:22Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1238202022-09-29T22:39:18Z Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading Eral, Huseyin Burak O'Mahony, Marcus Shaw, Robert M Trout, Bernhardt L. Myerson, Allan S. Doyle, Patrick S Massachusetts Institute of Technology. Department of Chemical Engineering Eral, Huseyin Burak Eral, Huseyin Burak , O’Mahony,Marcus; Shaw, Robert ; Trout, Bernhardt L. ; Myerson, Allan S. ; Doyle, Patrick S. Efficient control of crystallization and crystal properties still represents a bottleneck in the manufacturing of crystalline materials ranging from pigments to semiconductor particles. In the case of pharmaceutical drug manufacture, current methods for controlling critical crystal properties such as size and morphology that dictates the product’s efficacy are inefficient and often lead to the generation of undesirable solid states such as metastable polymorphs or amorphous forms. In this work, we propose an approach for producing crystals of a poorly water-soluble pharmaceutical compound embedded in a polymer matrix. Taking advantage of the composite hydrogel structure, we control the crystallization of the active pharmaceutical ingredient (API), within the composite hydrogel, generating crystalline API of controlled crystal size and loading. The composite hydrogels initially consist of organic phase droplets, acting as crystallization reactors, embedded in an elastic hydrogel matrix. By controlled evaporation of this composite material, crystals of controlled size (330 nm to 420 μm) and loading (up to 85%w/w) are produced. Through the interplay of elasticity and confinement, composite hydrogels control the crystal size and morphology via a two-step mechanism. First, the elastic matrix counteracts evaporation-induced coalescence of the emulsion droplets, keeping droplets isolated. Second, a confinement-induced elastic energy barrier, limits the growth of crystals beyond the size designated by the droplets. The proposed approach can be applied to production of a wide range of crystalline materials. 2020-02-18T19:02:10Z 2020-02-18T19:02:10Z 2014-10 2014-10 Article http://purl.org/eprint/type/JournalArticle 0897-4756 1520-5002 https://hdl.handle.net/1721.1/123820 Eral, Huyesin Burak et al. "Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading." Chemistry of Materials 26, 21 (October 2014): 6213-6220 © 2014 American Chemical Society en_US http://dx.doi.org/10.1021/cm502834h Chemistry of Materials Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf application/octet-stream application/octet-stream American Chemical Society (ACS) Huseyin Burak Eral |
| spellingShingle | Eral, Huseyin Burak O'Mahony, Marcus Shaw, Robert M Trout, Bernhardt L. Myerson, Allan S. Doyle, Patrick S Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading |
| title | Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading |
| title_full | Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading |
| title_fullStr | Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading |
| title_full_unstemmed | Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading |
| title_short | Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading |
| title_sort | composite hydrogels laden with crystalline active pharmaceutical ingredients of controlled size and loading |
| url | https://hdl.handle.net/1721.1/123820 |
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