Pair distribution function X-ray analysis explains dissolution characteristics of felodipine melt extrusion products.

Abstract:

:Solid solutions of felodipine with EUDRAGIT E and EUDRAGIT E/NE were shown to dramatically increase the dissolution rate of felodipine in biorelevant media. Of the two polymer systems, extrudates containing 5% EUDRAGIT NE showed a faster dissolution rate and less recrystallization (no precipitation within 2 h). Although differential scanning calorimetry (DSC) and conventional X-ray powder diffraction (XRPD) were able to verify the amorphous state of the drug after melt extrusion, it was not possible to differentiate the two extrudate compositions further with these methods. We then applied pair distribution function (PDF) analysis to investigate extrudates. It was possible to more closely characterize the solid state of the amorphous extrudates in terms of local structural order: PDF analysis revealed that addition of minor amounts of EUDRAGIT NE to the main component EUDRAGIT E during extrusion changed the local structure of EUDRAGIT E in a nonadditive way. We conclude that local ordering can be important to the release characteristics of extrudates, even when the components are present in the amorphous state.

journal_name

J Pharm Sci

authors

Nollenberger K,Gryczke A,Meier Ch,Dressman J,Schmidt MU,Brühne S

doi

10.1002/jps.21534

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1476-86

issue

4

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)32934-3

journal_volume

98

pub_type

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