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Solving the Delivery Problems of Triclabendazole Using Cyclodextrins.
AAPS PharmSciTech. 2018 Jul; 19(5):2311-2321.AP

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.

Authors+Show Affiliations

Instituto de Química de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Suipacha 531, 2000, Rosario, Argentina.Instituto de Química de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Suipacha 531, 2000, Rosario, Argentina. Departamento Farmacia, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.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.Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, Mississippi, 38677, USA.Instituto de Química de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Suipacha 531, 2000, Rosario, Argentina. csalomon@fbioyf.unr.edu.ar. Departamento Farmacia, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina. csalomon@fbioyf.unr.edu.ar.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29845501

Citation

Real, Daniel, et al. "Solving the Delivery Problems of Triclabendazole Using Cyclodextrins." AAPS PharmSciTech, vol. 19, no. 5, 2018, pp. 2311-2321.
Real D, Leonardi D, Williams RO, et al. Solving the Delivery Problems of Triclabendazole Using Cyclodextrins. AAPS PharmSciTech. 2018;19(5):2311-2321.
Real, D., Leonardi, D., Williams, R. O., Repka, M. A., & Salomon, C. J. (2018). Solving the Delivery Problems of Triclabendazole Using Cyclodextrins. AAPS PharmSciTech, 19(5), 2311-2321. https://doi.org/10.1208/s12249-018-1057-5
Real D, et al. Solving the Delivery Problems of Triclabendazole Using Cyclodextrins. AAPS PharmSciTech. 2018;19(5):2311-2321. PubMed PMID: 29845501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Solving the Delivery Problems of Triclabendazole Using Cyclodextrins. AU - Real,Daniel, AU - Leonardi,Darío, AU - Williams,Robert O,3rd AU - Repka,Michael A, AU - Salomon,Claudio J, Y1 - 2018/05/29/ PY - 2018/03/05/received PY - 2018/05/04/accepted PY - 2018/5/31/pubmed PY - 2018/10/3/medline PY - 2018/5/31/entrez KW - amorphous nature KW - cylodextrin KW - dissolution profiles KW - storage KW - triclabendazole SP - 2311 EP - 2321 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 19 IS - 5 N2 - 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. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/29845501/Solving_the_Delivery_Problems_of_Triclabendazole_Using_Cyclodextrins_ L2 - https://dx.doi.org/10.1208/s12249-018-1057-5 DB - PRIME DP - Unbound Medicine ER -