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Solving the Delivery Problems of Triclabendazole Using Cyclodextrins

AAPS PharmSciTech volume 19, pages 2311–2321 (2018)Cite this article

Abstract

Triclabendazole is the first-line drug of choice to treat and control fasciolasis, a neglected parasitic human disease. It is a class II/IV compound according to the Biopharmaceutics Classification System. Thus, the aim of this study was to improve aqueous solubility and dissolution rate of triclabendazole complexed with 2-hydroxylpropyl-β-cyclodextrin (HP-β-CD) and methyl-β-cyclodextrin (Me-β-CD) at 1:1 and 1:2 M ratio. The impact of storage on the solubility, dissolution profile, and solid-state properties of such complexes was also investigated. Drug-carrier interactions were characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. The solubility of triclabendazole improved up to 256- and 341-fold using HP-β-CD and Me-β-CD, respectively. In particular, the drug complexed with Me-β-CD showed a positive deviation from linearity, suggesting that its solubility increases with an increasing concentration of Me-β-CD concentration in a nonlinear manner. The drug dissolution was found to be improved through complex formation with HP-β-CD and Me-β-CD. In particular, the 1:2 M ratio complexes exhibited higher dissolution than the corresponding 1:1 M ratio complexes. The physicochemical characterization of the systems showed strong evidence of amorphous phases and/or of the formation of an inclusion complex. Stored at 25 °C, 60% RH for 24 months, drug complexed with β-cyclodextrins (CDs) at 1:2 M ratio remained amorphous. Based on these findings, it is postulated that the formation of triclabendazole-CD inclusion complexes produced significant enhancement in both the dissolution and solid-state properties of the drug, which may lead to the development of triclabendazole novel formulations with improved biopharmaceutical characteristics.

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Funding

DR, DL, and CJS gratefully acknowledge the Universidad Nacional de Rosario (Argentina) and CONICET (Argentina) for financial support. DR thanks CONICET (Argentina) for a Ph.D. fellowship.

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Affiliations

  1. Instituto de Química de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Suipacha 531, 2000, Rosario, Argentina

    Daniel Real, Darío Leonardi & Claudio J. Salomon

  2. Departamento Farmacia, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina

    Darío Leonardi & Claudio J. Salomon

  3. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, 2409 West University Avenue, PHR 4.214, Austin, Texas, 78712, USA

    Robert O. Williams III

  4. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, Mississippi, 38677, USA

    Michael A. Repka

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  1. Daniel Real
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  2. Darío Leonardi
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  3. Robert O. Williams III
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  4. Michael A. Repka
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  5. Claudio J. Salomon
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Correspondence to Claudio J. Salomon.

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Real, D., Leonardi, D., Williams, R.O. et al. Solving the Delivery Problems of Triclabendazole Using Cyclodextrins. AAPS PharmSciTech 19, 2311–2321 (2018). https://doi.org/10.1208/s12249-018-1057-5

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KEY WORDS

  • triclabendazole
  • cylodextrin
  • amorphous nature
  • dissolution profiles
  • storage