Thermal analysis used to guide the production of thymol and Lippia origanoides essential oil inclusion complexes with cyclodextrin

  • Felipe Q. Pires
  • Ludmila A. Pinho
  • Daniel O. Freire
  • Izabel C. R. Silva
  • Livia L. Sa-Barreto
  • Lucio Cardozo-Filho
  • Tais Gratieri
  • Guilherme M. Gelfuso
  • Marcilio Cunha-FilhoEmail author


This study aimed to use thermal analysis and other analytical tools to guide the production of thymol (TML) and essential oil of Lippia origanoides (EO) solid inclusion complexes from a screening of different cyclodextrins (CDs) types and production methods (freeze drying, spray drying, rotary evaporation and supercritical CO2). According to the phase solubility diagrams, the best complexation efficiency of TML was achieved using hydroxypropyl-β-cyclodextrin (~ 0.7), comparing to the natives CDs, which showed values below 0.5. Thermogravimetry was effective in evaluating the amount of drug inclusion complexes in each solid sample by measuring the evaporation of TML, which was dependent of its degree of interaction with the CD. Freeze drying was the most effective method in originating true inclusion complexes in solid state producing the encapsulation of nearly 70% of available TML which were stable at temperature ranges from 200 to 280 °C. Indeed, according to the stability assay, the shelf-life increase achieved for the TML standard was 354%, while the EO had a stability increase of around 45%. Finally, the antifungal effect against Candida albicans (ATCC 14053) was increased in complexed forms in about 1.5 times and 5.4 times for EO and TML, respectively, while the antifungal activity for Trichophyton mentagrophytes (ATCC 11481) was increased with TML and EO encapsulated with CD in more than 22 times and 45 times, respectively, compared to their free forms. Thus, the optimized inclusion complexes seem to be promising in pharmaceutical field for a future development of topical preparations containing TML and its natural substrates.


Antifungal activity Lippia origanoides essential oil Solid inclusion complex Stability Thermal analysis Thymol 



The authors would like to thank Professor Joyce da Silva from the Laboratory of Natural Products of the Federal University of Pará, Brazil, for kindly supplying the essential oil extracts used in this work. Additionally, the authors thank the valuable contribution of Daniela Galter and Karina Riccomini from Ashland Specialty Ingredients, who donated the CDs, and the Oswaldo Cruz Foundation (Fiocruz, Brazil) for providing the biological material.


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Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  • Felipe Q. Pires
    • 1
  • Ludmila A. Pinho
    • 1
  • Daniel O. Freire
    • 2
  • Izabel C. R. Silva
    • 2
  • Livia L. Sa-Barreto
    • 2
  • Lucio Cardozo-Filho
    • 3
    • 4
  • Tais Gratieri
    • 1
  • Guilherme M. Gelfuso
    • 1
  • Marcilio Cunha-Filho
    • 1
    Email author
  1. 1.Laboratory of Food, Drug and Cosmetics (LTMAC), School of Health SciencesUniversity of BrasíliaBrasíliaBrazil
  2. 2.School of CeilandiaUniversity of Brasília (UnB)CeilândiaBrazil
  3. 3.Department of Chemical EngineeringUniversidade Estadual de Maringá (UEM)MaringáBrazil
  4. 4.Centro Universitário da Fundação de Ensino Octávio Bastos (UNIFEOB)São João da Boa VistaBrazil

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