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Title: Local structure of ion pair interaction in lapatinib amorphous dispersions characterized by synchrotron x-ray diffraction and pair distribution function analysis

For many years, the idea of analyzing atom-atom contacts in amorphous drug-polymer systems has been of major interest, because this method has always had the potential to differentiate between amorphous systems with domains and amorphous systems which are molecular mixtures. In this study, local structure of ionic and noninonic interactions were studied by High-Energy X-ray Diffraction and Pair Distribution Function (PDF) analysis in amorphous solid dispersions of lapatinib in hypromellose phthalate (HPMCP) and hypromellose (HPMC-E3). The strategy of extracting lapatinib intermolecular drug interactions from the total PDF x-ray pattern was successfully applied allowing the detection of distinct nearest neighbor contacts for the HPMC-E3 rich preparations showing that lapatinib molecules do not cluster in the same way as observed in HPMC-P, where ionic interactions are present. Orientational correlations up to nearest neighbor molecules at about 4.3 Å were observed for polymer rich samples; both observations showed strong correlation to the stability of the systems. Lasty, the superior physical stability of 1:3 LP:HPMCP was consistent with the absence of significant intermolecular interactions in (ΔD inter LP(r)) in the range of 3.0 to 6.0 Å, which are attributed to C-C, C-N and C-O nearest neighbor contacts present in drug-drug interactions.
Authors:
 [1] ;  [2] ;  [3]
  1. Univ. of Sao Paulo, Sao Paulo (Brazil); Purdue Univ., West Lafayette, IN (United States)
  2. Argonne National Lab. (ANL), Argonne, IL (United States)
  3. Purdue Univ., West Lafayette, IN (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357
Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); Sao Paulo Research Foundation (FAPESP)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 36 MATERIALS SCIENCE; chemistry; materials science
OSTI Identifier:
1360151

de Araujo, Gabriel L. B., Benmore, Chris J., and Byrn, Stephen R.. Local structure of ion pair interaction in lapatinib amorphous dispersions characterized by synchrotron x-ray diffraction and pair distribution function analysis. United States: N. p., Web. doi:10.1038/srep46367.
de Araujo, Gabriel L. B., Benmore, Chris J., & Byrn, Stephen R.. Local structure of ion pair interaction in lapatinib amorphous dispersions characterized by synchrotron x-ray diffraction and pair distribution function analysis. United States. doi:10.1038/srep46367.
de Araujo, Gabriel L. B., Benmore, Chris J., and Byrn, Stephen R.. 2017. "Local structure of ion pair interaction in lapatinib amorphous dispersions characterized by synchrotron x-ray diffraction and pair distribution function analysis". United States. doi:10.1038/srep46367. https://www.osti.gov/servlets/purl/1360151.
@article{osti_1360151,
title = {Local structure of ion pair interaction in lapatinib amorphous dispersions characterized by synchrotron x-ray diffraction and pair distribution function analysis},
author = {de Araujo, Gabriel L. B. and Benmore, Chris J. and Byrn, Stephen R.},
abstractNote = {For many years, the idea of analyzing atom-atom contacts in amorphous drug-polymer systems has been of major interest, because this method has always had the potential to differentiate between amorphous systems with domains and amorphous systems which are molecular mixtures. In this study, local structure of ionic and noninonic interactions were studied by High-Energy X-ray Diffraction and Pair Distribution Function (PDF) analysis in amorphous solid dispersions of lapatinib in hypromellose phthalate (HPMCP) and hypromellose (HPMC-E3). The strategy of extracting lapatinib intermolecular drug interactions from the total PDF x-ray pattern was successfully applied allowing the detection of distinct nearest neighbor contacts for the HPMC-E3 rich preparations showing that lapatinib molecules do not cluster in the same way as observed in HPMC-P, where ionic interactions are present. Orientational correlations up to nearest neighbor molecules at about 4.3 Å were observed for polymer rich samples; both observations showed strong correlation to the stability of the systems. Lasty, the superior physical stability of 1:3 LP:HPMCP was consistent with the absence of significant intermolecular interactions in (ΔDinterLP(r)) in the range of 3.0 to 6.0 Å, which are attributed to C-C, C-N and C-O nearest neighbor contacts present in drug-drug interactions.},
doi = {10.1038/srep46367},
journal = {Scientific Reports},
number = ,
volume = 7,
place = {United States},
year = {2017},
month = {4}
}