Critical Excipient Properties for the Dissolution Enhancement of Phenytoin

Lindsay M. Johnson, Marc A. Hillmyer

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19116-19127
Number of pages12
JournalACS Omega
Volume4
Issue number21
DOIs
StatePublished - Nov 19 2019

PubMed: MeSH publication types

  • Journal Article

Fingerprint Dive into the research topics of 'Critical Excipient Properties for the Dissolution Enhancement of Phenytoin'. Together they form a unique fingerprint.

  • Cite this