Long-term stability of ivermectin nanosuspensions

TROVATO, G.; GONZALEZ VIDAL, N. L.; PALMA, S. D.; STARKLOFF, W. J.; BUCALÁ, V.

Rosario

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas; 2016

Universidad Nacional de Rosario - Universidad Nacional de Córdoba

In recent years, the development of new formulation strategies for poorly water-soluble active pharmaceutical ingredients (API) has focused on the study of nanometric systems. It has been proved that the reduction of API particle size, increase the dissolution rate and thus could improve oral bioavailability. High-pressure homogenization (HPH) is a milling technique frequently used to process hydrophobic APIs in aqueous media. Ivermectin (IVM) is an antiparasitic agent that exhibits a broad-spectrum activity, in veterinary and human therapy. It is a good candidate to formulate as nanosuspension (NS) due to its low aqueous solubility. NSs are thermodynamically unstable and the addition of adequate stabilizers are required. The aim of this work was to assess the long-term stability of IVM NSs obtained by HPH. The composition of the developed NS was IVM:Tween 80:Polyvinylpirrolidone (1:0.5:0.5 % w/v). NSs were characterized in terms of particle size distribution, dissolution rate, chemical stability (high performance liquid chromatography-HPLC) and crystalline state (differential scanning calorimetry-DSC, powder X-ray diffraction-PXRD), along two years of storage under natural aging conditions (25 °C and 60% of relative humidity). Median particle size (D50) results were 236±5, 330±1 and 301±7 nm for fresh NS, and after one and two years of storage, respectively. Even though this slight increase in D50, no statistically differences have been detected between dissolution profiles, compared via f2 similarity factor (with fresh IVM NS as reference). Furthermore, no statistically significant differences were observed in dissolution rate or kinetics constants. DSC and PXRD results indicate that IVM remained in amorphous state after storage. HPLC results indicate chemical stability of the NSs, since no significant differences were detected in IVM content, and no degradation peaks were observed.In conclusion, IVM NSs obtained by HPH are physicochemically stable for a period of two years, an attractive shelf life time for this formulation.