Effect of hydroxypropyl methylcellulose on beta cyclodextrin complexation of praziquantel in solution and in solid state

  • Layany Carolyny da Silva Mourão
  • Daiane Rafaela M. Ribeiro Batista
  • Sara Braga Honorato
  • Alejandro Pedro Ayala
  • Waldenice de Alencar Morais
  • Euzébio Guimarães Barbosa
  • Fernanda Nervo Raffin
  • Túlio Flávio Accioly de Lima e Moura
Original Article

Abstract

The effect of hydroxypropyl methylcellulose (HPMC) on complexation of praziquantel with beta cyclodextrin (PRZ–βCD) in solution and in the solid state was investigated. Phase solubility studies of βCD (0, 3, 6, 9 and 12 mmol L−1) were carried out by adding an excess amount of PRZ (8 mmol L−1) in the absence and presence of the polymer (with and without heating at 120 °C). Equimolar binary and ternary complexes were prepared by kneading and freeze-drying and characterized by DSC, DTA TGA, FTIR, XRPD and SEM patterns. A stoichiometry ratio of 1:1 was indicated by phase-solubility studies both in the presence and absence of 0.5 % HPMC. The molecular modeling confirms the 1:1 stoichiometry rate with Higuchi’s Al type. The presence of HPMC improved the complexation between PRZ and βCD by increases in both the intrinsic solubility of the drug as well as in values of the stability constant, complexation efficiency and Gibb’s free energy of the complex, principally in the presence of heating (up to ninefold relative to aqueous solubility of the drug). The synergic effect of HPMC was also observed in thermal analysis, with lower dehydration enthalpy for ternary complexes. The results of melting enthalpy were according to XRPD results, indicating that the preparation technique and presence of HPMC influenced thermal and crystallographic characteristics of inclusion complexes. The FTIR patterns suggest the complexation mechanism while SEM patterns showed the formation of inclusion complexes. The use of the HPMC and freeze-drying technique suggest more effective formation of PRZ:βCD inclusion complexes.

Keywords

Hydroxypropyl methylcellulose Beta cyclodextrin Praziquantel Inclusion complex Kneading Freeze-drying 

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Layany Carolyny da Silva Mourão
    • 1
  • Daiane Rafaela M. Ribeiro Batista
    • 1
  • Sara Braga Honorato
    • 2
  • Alejandro Pedro Ayala
    • 2
  • Waldenice de Alencar Morais
    • 1
  • Euzébio Guimarães Barbosa
    • 3
  • Fernanda Nervo Raffin
    • 1
  • Túlio Flávio Accioly de Lima e Moura
    • 1
  1. 1.Laboratory of Drug Development, Pharmacy Department, Health Sciences CenterFederal University of Rio Grande do NorteNatalBrazil
  2. 2.Laboratory of Vibrational Spectroscopy, Physics Department, Bloco 922, Sciences Center, Campus do PiciFederal University of CearáFortalezaBrazil
  3. 3.Laboratoty of Chemistry, Pharmacy Department, Health Sciences CenterFederal University of Rio Grande do NorteNatalBrazil

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