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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

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep46367· OSTI ID:1360151
 [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)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); Sao Paulo Research Foundation (FAPESP)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1360151
Journal Information:
Scientific Reports, Vol. 7; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 23 works
Citation information provided by
Web of Science

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Cited By (6)

Using X-ray Diffraction Techniques for Biomimetic Drug Development, Formulation, and Polymorphic Characterization journal December 2020
Characterization of amorphous solid dispersions journal October 2017
Force-sampling methods for density distributions as instances of mapped averaging journal January 2019
In situ solid-state NMR characterization of pharmaceutical materials: An example of drug-polymer thermal mixing journal January 2020
Striking the right balance of intermolecular coupling for high-efficiency singlet fission journal January 2018
Use of Terahertz-Raman Spectroscopy to Determine Solubility of the Crystalline Active Pharmaceutical Ingredient in Polymeric Matrices during Hot Melt Extrusion journal August 2019

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
36 MATERIALS SCIENCE
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