Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

  • Leticia Norma Carpentieri Rodrigues Universidade Federal de São Paulo, Instituto de Ciências Ambientais, Químicas e Farmacêuticas https://orcid.org/0000-0001-5175-859X
  • Anna Carollina Moraes Tavares Universidade Federal de São Paulo, Instituto de Ciências Ambientais, Químicas e Farmacêuticas
  • Beatriz Tavares Ferreira Universidade Federal de São Paulo, Instituto de Ciências Ambientais, Químicas e Farmacêuticas
  • Adriana Karla Cardoso Amorim Reis Universidade Federal de São Paulo, Instituto de Ciências Ambientais, Químicas e Farmacêuticas
  • Luciana Morita Katiki Secretaria de Agricultura e Abastecimento do Estado de São Paulo, Instituto de Zootecnia
Keywords: Cyclodextrins/pharmacokinetics, Benzimidazoles/administration & dosage, Inclusion complexes, Cyclodextrin aggregates, Drug liberation/drug effects, Antiparasitic agents/analysis, Albendazole/analysis, Fenbendazole/analysis

Abstract

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, β-cyclodextrin increased the solubility of albendazole from 0.4188 to ∼93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-β-cyclodextrin, on the other hand, increased solubility to ∼443.06 µg mL-1 (1058×) for albendazole and ∼159.36 μg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (∼591.22 µg mL-1 ) for albendazole and 1373× (∼144.66 µg mL-1 ) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-β-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1 H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates.

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Published
2019-12-05
How to Cite
Rodrigues, L., Tavares, A. C., Ferreira, B., Reis, A., & Katiki, L. (2019). Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles. Brazilian Journal of Pharmaceutical Sciences, 55, e17776. https://doi.org/10.1590/s2175-97902019000117776
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Articles