Compositional Analysis of Low Quantities of Phase Separation in Hot-Melt-Extruded Solid Dispersions: A Combined Atomic Force Microscopy, Photothermal Fourier-Transform Infrared Microspectroscopy, and Localised Thermal Analysis Approach

ABSTRACT Purpose To characterise phase separations in aged hot-melt-extruded solid dispersions at a micron to submicron scale. Methods Hot-melt-extruded felodipine and Eudragit ® E PO systems at a range of compositions were studied after a standard period of aging to allow phase separation to occur....

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutical research 2011-09, Vol.28 (9), p.2311-2326
Main Authors: Qi, Sheng, Belton, Peter, Nollenberger, Kathrin, Gryczke, Andreas, Craig, Duncan Q. M.
Format: Article
Language:English
Subjects:
Biochemistry
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Crystallization
Differential Thermal Analysis - methods
Dispersion
Dissolution
Felodipine - analysis
Felodipine - chemistry
General pharmacology
Hot Temperature
Medical Law
Medical sciences
Microscopy, Atomic Force
Pharmaceutical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacy
Phase Transition
Polymethacrylic Acids - analysis
Polymethacrylic Acids - chemistry
Research Paper
Scientific method
Solubility
Spectroscopy, Fourier Transform Infrared - methods
Tablets
Technology, Pharmaceutical - methods
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:ABSTRACT Purpose To characterise phase separations in aged hot-melt-extruded solid dispersions at a micron to submicron scale. Methods Hot-melt-extruded felodipine and Eudragit ® E PO systems at a range of compositions were studied after a standard period of aging to allow phase separation to occur. The samples were characterised using combined nano-thermal analysis, photothermal FTIR microspectroscopy coupled with pulsed force mode AFM as a novel characterisation approach. Result Crystalline felodipine presents in all formulations with drug loadings from 10–70% (w/w). In formulations with high drug loadings (50 and 70%), amorphous felodipine co-exists with crystalline forms, and higher drug concentration is observed in the centre compared to the outer surface of the extrudates. Drug crystal dimensions in extrudates with low drug loadings (10–30%) are small, in the micron to submicron range. We propose that uneven drug distribution is principally caused by processing-associated factors such as expansion of extrudates during extrusion. Conclusions We have demonstrated that the novel combined approach allows site-specific characterisation of the extruded systems and that drug distribution may be uneven across the extrudates, with concomitant implications for understanding stability and drug release behaviour.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-011-0461-2