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Pharmaceutical Research

, 36:105 | Cite as

A Single Hydrogen to Fluorine Substitution Reverses the Trend of Surface Composition Enrichment of Sorafenib Amorphous Solid Dispersion upon Moisture Exposure

  • Yuejie Chen
  • Huijun Chen
  • Shan Wang
  • Chengyu Liu
  • Feng QianEmail author
Research Paper
  • 17 Downloads

Abstract

Purpose

To reveal the underlying mechanism inducing the opposite trends of surface composition enrichment of spray dried amorphous solid dispersions (ASD) of sorafenib and regorafenib, two compounds only differ in hydrogen to fluorine substitution.

Methods

Sorafenib/PVP and regorafenib/PVP ASDs were prepared by spray drying. Morphology of ASDs was visually inspected and examined by SEM. The surface compositions of ASDs were analyzed by XPS. Glass transition temperature (Tg) of ASDs was determined by DSC. Water vapor sorption isotherms of ASDs were studied by moisture sorption analyzer. Molecular interaction between the drug and the polymer was analyzed by solution NMR.

Results

In 10% and 20% drug loading sorafenib/PVP ASDs, short time moisture exposure induced PVP enrichment on the surface, and the appearance of initial ASDs powder became gel-like after water uptake. While in 30% sorafenib/PVP and any regorafenib/PVP ASDs regardless of drug loading, moisture exposure induced surface drug enrichment, while their powder-like appearance and average particle size remained unchanged. Meanwhile, sorafenib/PVP had similar water vapor sorption isotherms as regorafenib/PVP, before and after moisture induced phase separation. NMR study demonstrated a hex atomic ring H-bonding interaction between the drug and PVP, with a 1:1 drug: monomer stoichiometry molar ratio, which persisted in sorafenib/PVP but not regorafenib/PVP system under 95%RH moisture.

Conclusions

Moisture exposure could lead to drug or polymer enrichment on the surface of ASDs, while the viability of drug-polymer interaction persisting in water environment contributed to such surface composition enrichment.

KEY WORDS

amorphous solid dispersion amorphous phase separation drug-polymer interaction physical stability surface composition 

ABBREVIATIONS

2D-NOESY

Two-dimensional nuclear Overhauser effect spectroscopy

ASD

Amorphous solid dispersion

DSC

Differential scanning calorimetry

Mw

Molecular weight

NMR

Nuclear magnetic resonance

PM-ASD

Physical mixture of ASD and pure polymer

PVP

Poly(vinyl pyrrolidone)

PXRD

Powder X-ray diffraction

SEM

Scanning electron microscopy

Tg

Glass transition temperature

Tm

Melting point

XPS

X-ray photoelectron spectroscopy

Notes

Supplementary material

11095_2019_2632_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, and Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education)Tsinghua UniversityBeijingPeople’s Republic of China

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