In vitro dissolution evaluation of Ivermectin nanosuspensions.

STARKLOFF W. J; GONZALEZ VIDAL N. L.; FETTER VANESSA; PALMA S. D

Córdoba

Congreso; Tercera Reunión Internacional de Ciencias Farmacéuticas - RICIFA 2014; 2014

Facultad de Ciencias Quimicas - UNC

The dissolution properties of a drug contained in a dosage form, have a great impact on its bioavailability. The dissolution rate is a function of drug intrinsic solubility and particle size. Ivermectin (IVM), a widely used antihelmintic agent, is a very poorly soluble drug; therefore its bioavailability could be compromised. Nanosizing the drug substance is one promising strategy to increase surface area and thus enhance dissolution rate and bioavailability. The aim of the present study was to evaluate in vitro dissolution rate of IVM nanosuspensions (NSs), developed by high pressure homogenization (HPH), and compare them with bulk IVM. The NSs consisted of IVM (1% w/v) and different stabilizer mixtures (Tween 80-Poloxamer 188; Tween 80-PVP; SLS-Poloxamer 188), at the same total concentration. NSs were obtained by HPH, at 800bar and 40 cycles of homogenization. Particle size analysis was carried out using photon correlation spectroscopy and laser diffraction. Dissolution studies were performed using apparatus 2, at 50rpm, with 900ml of USP phosphate buffer pH 5.8 (with 0.5% SLS). Samples were filtered (0.22μm filter) and analyzed by HPLC. The Z-size of NSs containing Tween 80 were between 174.6-218.1nm with a polidispersity index (PDI) of about 0.25-0.36; meanwhile for NSs prepared with SLS, the Z-size was 918.4nm (PDI 0.31). Bulk IVM showed a mean particle size of 233μm. Different dissolution profiles were recorded for NSs and IVM powder, with significant differences in terms of dissolution rate and Dissolution Efficiency (43.87% for bulk drug, and values between 67.18% and 90.88% for NSs). Besides, the NS formulated with SLS-Poloxamer 188 showed low dissolution percentages, because of IVM chemical degradation (confirmed by the appearance of degradation products in the chromatogram). The enhanced dissolution rate of IVM nanocrystals, particularly in the presence of Tween 80-PVP as stabilizer mixture, could be a promising approach for IVM oral delivery.