Improving the Dissolution of Triclabendazole from Stable Crystalline Solid Dispersions Formulated for Oral Delivery

REAL D.; ORZAN, L. ; LEONARDI D.; SALOMON C.

AAPS PHARMSCITECH

SPRINGER

Año: 2019 vol. 21

1530-9932

Triclabendazole belongs to the class II/IV of the Biopharmaceuticals Classification System, and its low aqueous solubility represents a major drawback during thedevelopment of effective dosage forms. Therefore, the goal of this study was to elucidatewhether polymeric solid dispersions would represent a suitable approach to overcome suchdisadvantage. Due to the lack of information on triclabendazole release, four differentdissolution media were evaluated to analyze drug dissolution rate. The polymeric soliddispersions were characterized by X-ray diffraction and Fourier transform infraredspectroscopy. The selected final formulations were further stored for 24 months, and theirphysical stability was evaluated by means of X-ray diffraction and drug dissolution assays.Drug solubility studies indicated that poloxamer 407 (P407) solubilized a higher amount ofdrug than polyethylene glycol 6000. Drug-to-carrier ratio, nature of the selected carriers, andthe type of dissolution media were important factors for increasing dissolution. By infraredspectroscopy, there were no specific interactions between the drug and polymers. Thephysicochemical characterization of the systems showed a detectable evidence of drugamorphization by increasing the carrier ratio. Micromeritic studies indicated that rawtriclabendazole, physical mixtures, and reference formulation showed poor flow properties, incontrast to the triclabendazole:P407 solid dispersion sample. Both the crystalline propertiesand dissolution rate of selected samples were very similar after 24 months at roomtemperature. Thus, considering physical stability and dissolution studies, the developmentof the solid dispersion is a very suitable methodology to improve triclabendazole dissolutionand, potentially, its biopharmaceutical performance.