Property prediction and pharmacokinetic evaluation of mixed stoichiometry cocrystals of zafirlukast, a drug delivery case study

Cocrystals have been identified as a method for ensuring the delivery of poorly soluble drugs. Development of cocrystal phases presents many challenges, with the in vivo drug delivery benefits difficult to predict robustly. Additional to this, many of the benefits seen in the literature do not use f...

Full description

Saved in:
Bibliographic Details
Published in:CrystEngComm 2018, Vol.20 (10), p.1346-1351
Main Authors: Corner, Philip A., Berry, David J., McCabe, James F., Barbas, Rafael, Prohens, Rafel, Du, Hongwen, Zhou, Hongyu, Llinas, Antonio
Format: Article
Language:English
Subjects:
Case studies
Drug delivery systems
Pharmacokinetics
Pharmacology
Predictions
Stoichiometry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cocrystals have been identified as a method for ensuring the delivery of poorly soluble drugs. Development of cocrystal phases presents many challenges, with the in vivo drug delivery benefits difficult to predict robustly. Additional to this, many of the benefits seen in the literature do not use formulation strategies which are representative of the clinical dosage form. Zafirlukast has been shown to possess poor development properties. It is poorly soluble and difficult to manufacture. Here we present a case study highlighting the benefits of cocrystals in this context, outlining the discovery, formulation and improved pharmacokinetics of mixed stoichiometry cocrystals of zafirlukast. This case study outlines methods, which could be broadly applied to other drug molecules, for determination of the properties of cocrystals through a suite of in vitro experiments that display a predictive pathway from physical form discovery to enhanced in vivo activity in animal models.
ISSN:1466-8033
1466-8033
DOI:10.1039/C7CE02059G