Determination of Ivermectin solubility in different stabilizer solutions and temperatures

STARKLOFF, W. J.; GONZALEZ VIDAL, N. L.; BUCALA, V.; PALMA, S. D.

Cordoba

Congreso; 3º Reunion Internacional de Ciencias Farmaceuticas; 2014

Universidad Nacional de Rosario - Universidad Nacional de Cordoba

Ivermectin (IVM), a widely used antihelmintic agent, presents a very low aqueous solubility, which lead to an erratic bioavailability and great intra-individual variations. One of the possibilities for improving its dissolution rate is to develop nanosuspensions, through high pressure homogeneization. Some critical points of this technique are the proper selection of the stabilizers and the concentration of the drug. Furthermore, the size and stability of nanosuspensions are dependent on the drug solubility in stabilizer solutions. Therefore, the aim of the present study was to determine the solubility of IVM in different stabilizer solutions, in order to assure supersaturation conditions in the subsequent nanosuspension development. Surfactant (polysorbate 80 and SLS-sodium lauryl sulfate) and polymeric (polyvinylpyrrolidone and poloxamer 188) agents were selected as stabilizers. Stabilizer solutions were prepared in triple distilled water, at two concentrations and different binary mixtures, combining a surfactant with a polymer (final concentration 1% and 2% w/v). The solubility of IVM in water and aqueous stabilizer solutions was determined by addition of an excess of the drug to the solvent (n=3). The mixture was stirred in a thermostatic bath (at 25° and 40° C) for 72 hours, centrifugated, filtered and assayed by UV-spectrophotometry (245nm). IVM solubility in triple distilled water was around 1 and 3 ug/ml, at 25° and 40° C, respectively. Solubility values were increased by 1000 to 2000 times when polysorbate was used as the surfactant component of the stabilizer binary mixture, with a significant temperature influence. When SLS was used, in combination with polymers, solubility values were increased by 5000 to 10000 times, regardless of the temperature. Furthermore, the IVM solubilities were exactly doubled when SLS concentration was duplicated. Formulation of IVM nanosuspensions at concentrations of 1% or 2% (w/v), in a 1:1 relationship with the stabilizer, assures a supersaturated system for nanosuspension development.