An investigation into the possibility of molecular inclusion complexation of indomethacin with starch by the alkaline method

  • Anna Marinopoulou
  • Dimitrios Christofilos
  • John Arvanitidis
  • Stylianos N. RaphaelidesEmail author
Original Article


Starch systems containing indomethacin were prepared by the alkaline method and characterized in order to investigate the potential of this method to produce amylose molecular inclusion complexes as targeted and controlled drug delivery carriers. Three types of starches with different amylose/amylopectin composition were used to prepare the systems. Their structure was probed by X-ray diffraction (XRD) and Raman spectroscopy, whereas their morphology was investigated by Optical microscopy and Confocal laser scanning microscopy (CLSM). Raman spectroscopy revealed the presence of p-chlorobenzoic acid, the degradation product of the alkaline hydrolysis of indomethacin in the matrix of the starch systems. The results were confirmed by XRD measurements and the degree of crystallinity of the starch systems ranged from 35 to 90%. In vitro release testing of indomethacin from the starch systems in the simulated gastric and small intestine fluid showed very low concentrations of indomethacin. CLSM micrographs and optical microscopic examination revealed the presence mostly of the p-chlorobenzoic acid, in the matrix of the starch systems, rather than of indomethacin. The results, in general, indicated that the p-chlorobenzoic acid molecules were either included in the amylose helices or they have been entrapped between the helices of the complexed amylose whereas the few indomethacin molecules present in the starch matrix probably were also mechanically entrapped.


Alkaline technique Inclusion complexes Indomethacin p-Chlorobenzoic acid Starch Raman spectroscopy 



The financial support of Dr. Marinopoulou through a postdoctoral fellowship granted by the Greek State Foundation of Scholarships (IKY) is gratefully acknowledged. The scholarship was funded by the "Enhancement of Post-graduate Researchers” Program, from the resources of the OP “Human Resources Development, Education and Lifelong Learning” with Priority Axes 6, 8, 9 and co-financed by the European Social Fund-(ESF) and the Greek government. Authors also acknowledge the Center for Interdisciplinary Research and Innovation of the Aristotle University of Thessaloniki (CIRI-AUTH) for the use of Raman instrumentation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Anna Marinopoulou
    • 1
  • Dimitrios Christofilos
    • 2
  • John Arvanitidis
    • 3
  • Stylianos N. Raphaelides
    • 1
    Email author
  1. 1.Central Research Laboratory for the Physical and Chemical Testing of Foods, Department of Food TechnologyATEI of ThessalonikiThessalonikiGreece
  2. 2.School of Chemical EngineeringAristotle University of ThessalonikiThessalonikiGreece
  3. 3.Physics DepartmentAristotle University of ThessalonikiThessalonikiGreece

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