Faculty Collaboration Database

Role of the Strength of Drug-Polymer Interactions on the Molecular Mobility and Crystallization Inhibition in Ketoconazole Solid Dispersions. Mol Pharm 2015 Sep 08;12(9):3339-50

Date

06/14/2015

Pubmed ID

26070543

DOI

10.1021/acs.molpharmaceut.5b00333

Scopus ID

2-s2.0-84941101436 (requires institutional sign-in at Scopus site)   145 Citations

Abstract

The effects of specific drug-polymer interactions (ionic or hydrogen-bonding) on the molecular mobility of model amorphous solid dispersions (ASDs) were investigated. ASDs of ketoconazole (KTZ), a weakly basic drug, with each of poly(acrylic acid) (PAA), poly(2-hydroxyethyl methacrylate) (PHEMA), and polyvinylpyrrolidone (PVP) were prepared. Drug-polymer interactions in the ASDs were evaluated by infrared and solid-state NMR, the molecular mobility quantified by dielectric spectroscopy, and crystallization onset monitored by differential scanning calorimetry (DSC) and variable temperature X-ray diffractometry (VTXRD). KTZ likely exhibited ionic interactions with PAA, hydrogen-bonding with PHEMA, and weaker dipole-dipole interactions with PVP. On the basis of dielectric spectroscopy, the α-relaxation times of the ASDs followed the order: PAA > PHEMA > PVP. In addition, the presence of ionic interactions also translated to a dramatic and disproportionate decrease in mobility as a function of polymer concentration. On the basis of both DSC and VTXRD, an increase in strength of interaction translated to higher crystallization onset temperature and a decrease in extent of crystallization. Stronger drug-polymer interactions, by reducing the molecular mobility, can potentially delay the crystallization onset temperature as well as crystallization extent.

Author List

Mistry P, Mohapatra S, Gopinath T, Vogt FG, Suryanarayanan R

Author

Gopinath Tata PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acrylic Resins
Calorimetry, Differential Scanning
Crystallization
Drug Interactions
Drug Stability
Hydrogen Bonding
Ketoconazole
Methacrylates
Phase Transition
Polymers
Povidone
Spectroscopy, Fourier Transform Infrared
X-Ray Diffraction