Particle size analysis of praziquantel formulations obtained by high pressure homogenization

GONZALEZ A; ´GONZALEZ VIDAL N; RAMÍREZ RIGO MV.

Rosario

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2016); 2016

Universidad de Rosario y UNC

High-pressure homogenization (HPH)is an established technique to prepare nanosuspensions (NSs) of many poorly water soluble drugs. The particle size reduction in the nanometric scale enhances the drug dissolution rate and bioavailability. The final particle size distribution depends on the drug, the number of cycles and the pressure of the homogenization process, and the correct stabilizer selection.Praziquantel (PZQ) is a widely used antihelmintic drug that exhibit very low aqueous solubility.Therefore, the aim of this work was to study the effect of different stabilizers, on the particle size distribution of PZQ NSs obtained by HPH.An aqueous PZQ dispersion (1% w/v) was preparedwith Poloxamer 188 (P188),either as unique stabilizer(0.25, 0.5,1% w/v) or as a part of binary mixtures(1% w/v) with other polymer (polyvinilpirrolidone or MD-maltodextrin) or surfactant (sodium lauryl sulphate). These dispersions were pre-homogenized (22000rpm, 10 minutes) andprocessed by HPH (60 cycles, 950 bar). The particle size distribution was characterized by photon correlation spectroscopy, in terms ofmean hydrodynamic diameter (Z-size),polydispersity index (PDI), and cumulative distribution values (D50, D90, D95).The particle size of raw PZQ was determined by laser diffraction.PZQ rawmaterialexhibited a volume mean diameter of 42.1µm. With the exception of the NSs prepared with P188 (0.25% w/v), the Z-sizeof the NSs were all below 710 nm, indicating a clear reduction of PZQ particle size to the nanometer range.Regarding to binary formulations, P188-MD showed the more suitablesizedistribution, with a D95 of 711.8 nm, a Z-size of 544.8 nm and a PDI of 0.47. Although other critical parameters need to be evaluated, in order to select a promising formulation, the analysis performed indicated that HPH is a useful methodology for the PZQ particle size reduction, and the formulation of choice would be PZQ-P188-MD.