title: 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.
authors.affiliation: a Departamento de Biología, Bioquímica y Farmacia , Universidad Nacional del Sur (UNS) , Bahía Blanca , Argentina.|b Planta Piloto de Ingeniería Química (PLAPIQUI), UNS-CONICET , Bahía Blanca , Argentina.
authors.forename: Walter Javier
authors.identifier: http://orcid.org/0000-0002-5111-4353
authors.initials: WJ
authors.lastname: Starkloff
authors.affiliation: b Planta Piloto de Ingeniería Química (PLAPIQUI), UNS-CONICET , Bahía Blanca , Argentina.
authors.forename: Verónica
authors.identifier: http://orcid.org/0000-0002-5707-4436
authors.initials: V
authors.lastname: Bucalá
authors.affiliation: c Departamento de Farmacia, Facultad de Ciencias Químicas , Universidad Nacional de Córdoba, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA) , Córdoba , Argentina.
authors.forename: Santiago Daniel
authors.identifier: http://orcid.org/0000-0003-4468-1111
authors.initials: SD
authors.lastname: Palma
authors.affiliation: a Departamento de Biología, Bioquímica y Farmacia , Universidad Nacional del Sur (UNS) , Bahía Blanca , Argentina.|d Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Bahía Blanca , Argentina.
authors.forename: Noelia L
authors.identifier: http://orcid.org/0000-0002-0687-0096
authors.initials: NL
authors.lastname: Gonzalez Vidal
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D015195:Drug Design; D006801:Humans; D007559:Ivermectin; D053758:Nanoparticles; D010316:Particle Size; D020442:Poloxamer; D012995:Solubility
chemical_list: D020442:Poloxamer; D007559:Ivermectin
keywords: Antihelmintics; dissolution rate; high pressure homogenization; nanosuspensions; solubility; stability