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Critical Excipient Properties for the Dissolution Enhancement of Phenytoin

[Image: see text] Solubility-enhancing amorphous solid dispersions can aid in the oral delivery of hydrophobic, poorly soluble drugs. Effective solid dispersion excipients enable high supersaturation drug concentrations over biologically relevant time scales. The critical characteristics of an excip...

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Autores principales: Johnson, Lindsay M., Hillmyer, Marc A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868594/
https://www.ncbi.nlm.nih.gov/pubmed/31763534
http://dx.doi.org/10.1021/acsomega.9b02383
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author Johnson, Lindsay M.
Hillmyer, Marc A.
author_facet Johnson, Lindsay M.
Hillmyer, Marc A.
author_sort Johnson, Lindsay M.
collection PubMed
description [Image: see text] Solubility-enhancing amorphous solid dispersions can aid in the oral delivery of hydrophobic, poorly soluble drugs. Effective solid dispersion excipients enable high supersaturation drug concentrations over biologically relevant time scales. The critical characteristics of an excipient that allow it to work well in a solid dispersion system are not well understood. We prepared poly(N-isopropylacrylamide), poly(N,N-dimethylacrylamide), and poly(N-hydroxyethylacrylamide) excipients of varying molar mass and examined their ability to improve the aqueous solubility of phenytoin, a Biopharmaceutical Class System Class II drug. Binary and ternary solid dispersions of phenytoin and these excipients, along with hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose, were prepared at 10 wt % drug loading. Dissolution behavior was studied at early time points (<1 min) and over the course of 6 h. Performance of the ternary solid dispersions was largely a function of the concentration of poly(N-isopropylacrylamide) present in micellar structures and the concentration of PNiPAm micelles in the dissolution media. We present several systems that achieved significant improvement of phenytoin solubility over a wide composition range at enhancement factors among the highest seen to date for phenytoin.
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spelling pubmed-68685942019-11-22 Critical Excipient Properties for the Dissolution Enhancement of Phenytoin Johnson, Lindsay M. Hillmyer, Marc A. ACS Omega [Image: see text] Solubility-enhancing amorphous solid dispersions can aid in the oral delivery of hydrophobic, poorly soluble drugs. Effective solid dispersion excipients enable high supersaturation drug concentrations over biologically relevant time scales. The critical characteristics of an excipient that allow it to work well in a solid dispersion system are not well understood. We prepared poly(N-isopropylacrylamide), poly(N,N-dimethylacrylamide), and poly(N-hydroxyethylacrylamide) excipients of varying molar mass and examined their ability to improve the aqueous solubility of phenytoin, a Biopharmaceutical Class System Class II drug. Binary and ternary solid dispersions of phenytoin and these excipients, along with hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose, were prepared at 10 wt % drug loading. Dissolution behavior was studied at early time points (<1 min) and over the course of 6 h. Performance of the ternary solid dispersions was largely a function of the concentration of poly(N-isopropylacrylamide) present in micellar structures and the concentration of PNiPAm micelles in the dissolution media. We present several systems that achieved significant improvement of phenytoin solubility over a wide composition range at enhancement factors among the highest seen to date for phenytoin. American Chemical Society 2019-11-06 /pmc/articles/PMC6868594/ /pubmed/31763534 http://dx.doi.org/10.1021/acsomega.9b02383 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Johnson, Lindsay M.
Hillmyer, Marc A.
Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
title Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
title_full Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
title_fullStr Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
title_full_unstemmed Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
title_short Critical Excipient Properties for the Dissolution Enhancement of Phenytoin
title_sort critical excipient properties for the dissolution enhancement of phenytoin
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868594/
https://www.ncbi.nlm.nih.gov/pubmed/31763534
http://dx.doi.org/10.1021/acsomega.9b02383
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