Correlation of Inhibitory Effects of Polymers on Indomethacin Precipitation in Solution and Amorphous Solid Crystallization Based on Molecular Interaction View Full Text


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Article Info

DATE

2014-02

AUTHORS

Harsh Chauhan, Anuj Kuldipkumar, Timothy Barder, Ales Medek, Chong-Hui Gu, Eman Atef

ABSTRACT

PURPOSE: To correlate the polymer's degree of precipitation inhibition of indomethacin in solution to the amorphous stabilization in solid state. METHODS: Precipitation of indomethacin (IMC) in presence of polymers was continuously monitored by a UV spectrophotometer. Precipitates were characterized by PXRD, IR and SEM. Solid dispersions with different polymer to drug ratios were prepared using solvent evaporation. Crystallization of the solid dispersion was monitored using PXRD. Modulated differential scanning calorimetry (MDSC), IR, Raman and solid state NMR were used to explore the possible interactions between IMC and polymers. RESULTS: PVP K90, HPMC and Eudragit E100 showed precipitation inhibitory effects in solution whereas Eudragit L100, Eudragit S100 and PEG 8000 showed no effect on IMC precipitation. The rank order of precipitation inhibitory effect on IMC was found to be PVP K90 > Eudragit E100 > HPMC. In the solid state, polymers showing precipitation inhibitory effect also exhibited amorphous stabilization of IMC with the same rank order of effectiveness. IR, Raman and solid state NMR studies showed that rank order of crystallization inhibition correlates with strength of molecular interaction between IMC and polymers. CONCLUSIONS: Correlation is observed in the polymers ability to inhibit precipitation in solution and amorphous stabilization in the solid state for IMC and can be explained by the strength of drug polymer interactions. More... »

PAGES

500-515

References to SciGraph publications

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  • 2009-12. Effects of Polymer Type and Storage Relative Humidity on the Kinetics of Felodipine Crystallization from Amorphous Solid Dispersions in PHARMACEUTICAL RESEARCH
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  • 2010-04. Understanding the Behavior of Amorphous Pharmaceutical Systems during Dissolution in PHARMACEUTICAL RESEARCH
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  • 2010-05. Influence of Preparation Methods on Solid State Supersaturation of Amorphous Solid Dispersions: A Case Study with Itraconazole and Eudragit E100 in PHARMACEUTICAL RESEARCH
  • 2009-01. Estimation of Drug–Polymer Miscibility and Solubility in Amorphous Solid Dispersions Using Experimentally Determined Interaction Parameters in PHARMACEUTICAL RESEARCH
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s11095-013-1178-1

    DOI

    http://dx.doi.org/10.1007/s11095-013-1178-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1000660789

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24122167


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