Formulation of liquid propofol as a cocrystalline solid

Scott C. McKellar, Alan R. Kennedy, Neil C. McCloy, Eileen McBride, Alastair J. Florence

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

This work details a crystal engineering strategy to obtain a novel solid form of the liquid drug molecule propofol using isonicotinamide as a cocrystal former. Knowledge of intermolecular hydrogen bonded supramolecular synthons has been exploited to select a potential cocrystal former based on the likely growth unit formed. The structure of the cocrystal, solved using single-crystal X-ray diffraction, is reported, confirming the molecular packing and key intermolecular interactions adopted in the novel solid form. The potential to enhance a drug’s properties is demonstrated by an increased melting point compared to the native drug form, such that the liquid drug becomes a stable solid at room temperature. Unusually, the propofol/isonicotinamide complex has three structurally similar, temperature-dependent polymorphs, and the crystal structure of each form is reported herein.
LanguageEnglish
Pages2422-2430
Number of pages9
JournalCrystal Growth and Design
Volume14
Issue number5
Early online date27 Feb 2014
DOIs
Publication statusPublished - 27 Feb 2014

Fingerprint

Propofol
drugs
formulations
Liquids
liquids
Crystal engineering
Pharmaceutical Preparations
Polymorphism
Melting point
Crystal structure
Single crystals
melting points
Hydrogen
X ray diffraction
Temperature
Molecules
engineering
crystal structure
single crystals
room temperature

Keywords

  • liquid propofol
  • solid crystalline powder
  • solid drug forms
  • crystal structure

Cite this

McKellar, Scott C. ; Kennedy, Alan R. ; McCloy, Neil C. ; McBride, Eileen ; Florence, Alastair J. / Formulation of liquid propofol as a cocrystalline solid. In: Crystal Growth and Design. 2014 ; Vol. 14, No. 5. pp. 2422-2430.
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Formulation of liquid propofol as a cocrystalline solid. / McKellar, Scott C.; Kennedy, Alan R.; McCloy, Neil C.; McBride, Eileen; Florence, Alastair J.

In: Crystal Growth and Design, Vol. 14, No. 5, 27.02.2014, p. 2422-2430.

Research output: Contribution to journalArticle

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T1 - Formulation of liquid propofol as a cocrystalline solid

AU - McKellar, Scott C.

AU - Kennedy, Alan R.

AU - McCloy, Neil C.

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AB - This work details a crystal engineering strategy to obtain a novel solid form of the liquid drug molecule propofol using isonicotinamide as a cocrystal former. Knowledge of intermolecular hydrogen bonded supramolecular synthons has been exploited to select a potential cocrystal former based on the likely growth unit formed. The structure of the cocrystal, solved using single-crystal X-ray diffraction, is reported, confirming the molecular packing and key intermolecular interactions adopted in the novel solid form. The potential to enhance a drug’s properties is demonstrated by an increased melting point compared to the native drug form, such that the liquid drug becomes a stable solid at room temperature. Unusually, the propofol/isonicotinamide complex has three structurally similar, temperature-dependent polymorphs, and the crystal structure of each form is reported herein.

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