Design and in vitro characterization of ivermectin nanocrystals liquid formulation based on a top–down approach

Abstract

The aim of this study was to develop ivermectin (IVM) nanosuspensions (NSs) to improve the dissolution rate of this poorly water-soluble drug. Different NSs combining different stabilizers, i.e. poloxamer 188 (P188), polysorbate 80 (T80), polyvinylpyrrolidone (PVP), and sodium lauryl sulfate (SLS), were prepared by high-pressure homogenization. The stabilizers were selected based on the saturation solubility and IVM stability within 72 h. The screening of formulations was performed by considering the drug content within the nanosize range. The best formulation (IVM:T80:PVP 1:0.5:0.5 wt%) was characterized in terms of the particle size distribution, morphology, crystallinity, drug content, and in vitro dissolution profile. This NS was also evaluated from a stability point of view, by conditioning samples at a constant temperature and relative humidity for six months. The fresh and conditioned best NSs Z-sizes were 174.6 and 215.7 nm, respectively; while both NSs showed low polydispersity indexes. The faster dissolution rate for the IVM NS was attributed to the presence of nanoparticles and changes to the crystal structure (i.e. amorphization) that further improved solubility. The best NS had a 4-fold faster initial dissolution rate than raw IVM, and is thus a promising formulation for the treatment of human and animal parasitic diseases.

Keywords:

• Antihelmintics
• dissolution rate
• high pressure homogenization
• nanosuspensions
• solubility
• stability

Acknowledgements

The authors kindly thank Graciela Mas (Universidad Nacional del Sur, CONICET), Fernanda Cabrera (CONICET), and María Julia Yañez (CONICET) for their technical assistance with X-ray diffraction, DSC, and SEM analyses, respectively. The authors would like to thank Vanessa Fetter for collaboration with dissolution studies.

Disclosure statement

The authors report no declarations of interest.

Funding

Walter J. Starkloff is a doctoral fellowship holder of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina). This work was supported by Universidad Nacional del Sur (PGI 24/ZB56) and CONICET (PIP CONICET 112 201101 00336).