Solving the Delivery Problems of Triclabendazole Using Cyclodextrins.

REAL D.; LEONARDI D.; WILLIAMS, R; REPKA, M.; SALOMON C.

AAPS PHARMSCITECH

SPRINGER

Lugar: Berlin; Año: 2018 vol. 19 p. 2311 - 2321

1530-9932

Triclabendazole is the first-line drug of choice to treat and control fasciolasis, aneglected parasitic human disease. It is a class II/IV compound according to theBiopharmaceutics Classification System. Thus, the aim of this study was to improve aqueoussolubility 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. Theimpact of storage on the solubility, dissolution profile, and solid-state properties of suchcomplexes was also investigated. Drug-carrier interactions were characterized by infraredspectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electronmicroscopy. 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 apositive deviation from linearity, suggesting that its solubility increases with an increasingconcentration of Me-β-CD concentration in a nonlinear manner. The drug dissolution wasfound to be improved through complex formation with HP-β-CD and Me-β-CD. Inparticular, the 1:2 M ratio complexes exhibited higher dissolution than the corresponding1:1 M ratio complexes. The physicochemical characterization of the systems showed strongevidence of amorphous phases and/or of the formation of an inclusion complex. Stored at25 °C, 60% RH for 24 months, drug complexed with β-cyclodextrins (CDs) at 1:2 M ratioremained amorphous. Based on these findings, it is postulated that the formation oftriclabendazole-CD inclusion complexes produced significant enhancement in both thedissolution and solid-state properties of the drug, which may lead to the development oftriclabendazole novel formulations with improved biopharmaceutical characteristics