Pharmaceutical Research

, Volume 31, Issue 10, pp 2887–2903 | Cite as

Enhancement of the Physical Stability of Amorphous Indomethacin by Mixing it with Octaacetylmaltose. Inter and Intra Molecular Studies

  • E. KaminskaEmail author
  • K. Adrjanowicz
  • D. Zakowiecki
  • B. Milanowski
  • M. Tarnacka
  • L. Hawelek
  • M. Dulski
  • J. Pilch
  • W. Smolka
  • I. Kaczmarczyk-Sedlak
  • K. Kaminski
Research Paper



To demonstrate a very effective and easy way of stabilization of amorphous indomethacin (IMC) by preparing binary mixtures with octaacetylmaltose (acMAL). In order to understand the origin of increased stability of amorphous system inter- and intramolecular interactions between IMC and acMAL were studied.


The amorphous IMC, acMAL and binary mixtures (IMC–acMAL) with different weight ratios were analyzed by using Dielectric Spectroscopy (DS), Differential Scanning Calorimetry (DSC), Raman Spectroscopy, X-ray Diffraction (XRD), Infrared Spectroscopy (FTIR) and Quantitative Structure–Activity Relationship (QSAR).


Our studies have revealed that indomethacin mixed with acetylated saccharide forms homogeneous mixture. Interestingly, even a small amount of modified maltose prevents from recrystallization of amorphous indomethacin. FTIR measurements and QSAR calculations have shown that octaacetylmaltose significantly affects the concentration of indomethacin dimers. Moreover, with increasing the amount of acMAL in the amorphous solid dispersion molecular interactions between matrix and API become more dominant than IMC-IMC ones. Structural investigations with the use of X-ray diffraction technique have demonstrated that binary mixture of indomethacin with acMAL does not recrystallize upon storage at room temperature for more than 1.5 year. Finally, it was shown that acMAL can be used to improve solubility of IMC.


Acetylated derivative of maltose might be very effective agent to improve physical stability of amorphous indomethacin as well as to enhance its solubility. Intermolecular interactions between modified carbohydrate and IMC are likely to be responsible for increased stability effect in the glassy state.


crystallization glass transition indomethacin intermolecular interactions molecular dynamics octaacetylmaltose physical stability 



E.K., M.T., M.D. are thankful for the financial support from the National Center of Science based on decision DEC-2013/09/D/NZ7/04194. The authors are also thankful to Dr. M. Kopras from GlaxoSmithKline Pharmaceuticals S.A. (Poznan, Poland) for providing indomethacin. We would like to thank Dr M. Jarek from NanoBioMedical Centre (Poznan, Poland) for performing DSC measurements.

This research was supported in part by PL-Grid Infrastructure.


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© Springer Science+Business Media New York 2014

Authors and Affiliations

  • E. Kaminska
    • 1
    Email author
  • K. Adrjanowicz
    • 2
  • D. Zakowiecki
    • 3
  • B. Milanowski
    • 4
  • M. Tarnacka
    • 5
  • L. Hawelek
    • 5
    • 6
  • M. Dulski
    • 5
  • J. Pilch
    • 7
  • W. Smolka
    • 8
  • I. Kaczmarczyk-Sedlak
    • 1
  • K. Kaminski
    • 5
  1. 1.Medical University of Silesia in Katowice, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Department of Pharmacognosy and PhytochemistrySosnowiecPoland
  2. 2.NanoBioMedical CentreAdam Mickiewicz UniversityPoznanPoland
  3. 3.Pharmaceutical Works Polpharma SAStarogard GdanskiPoland
  4. 4.Department of Pharmaceutical TechnologyPoznan University of Medical SciencesPoznanPoland
  5. 5.Institute of PhysicsSilesian UniversityKatowicePoland
  6. 6.Institute of Non-ferrous MetalsGliwicePoland
  7. 7.Department of Biological SciencesAcademy of Physical EducationKatowicePoland
  8. 8.Department of LaryngologyMedical University of SilesiaKatowicePoland

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