Solubility determination of Praziquantel in polymeric and surfactant solutions

GONZALEZ, M.A.; RAMIREZ RIGO, M.V.; GONZALEZ VIDAL, N. L.

Rosario

Congreso; 4º Reunión Internacional de Ciencias Farmacéuticas; 2016

Universidad Nacional de Rosario - Universidad Nacional de Cordoba

Praziquantel (PZQ) is an antihelmintic drug, effective against a broad range of trematodes and cestodes. It has a very low aqueous solubility, leading to erratic absorption and low bioavailability. A possible approach for overcoming this issue is to increase drug surface area by preparing nanosuspensions, through high pressure homogenization (HPH). This methodology is sensitive to the proper selection of stabilizers and drug concentration. Therefore, the aim of this study was to determine the PZQ solubility in different stabilizer solutions, in order to assure supersaturation conditions for the nanosuspension development by HPH.Surfactant (P80-Polysorbate 80 and SLS-sodium lauryl sulfate) and polymeric (PVP-Polyvinylpyrrolidone, P188-Poloxamer 188, HPMC-Hypromellose and MD-Maltodextrin) agents were selected as stabilizers. Binary solutions (surfactant-polymer or polymer-polymer) were prepared in triple distilled water, being the total stabilizer concentration of 1% (w/v). Moreover, P188 was used, individually, at different concentrations (0.25%, 0.5%, 1% w/v). The solubility was determined by addition of an excess of PZQ to the solvent (n=3). The mixture was stirred in a thermostatic bath at 40° C (the highest temperature reached by the dispersion during the HPH process) for 96 hours. Subsequently, samples were centrifugated, filtered and assayed by UV-spectrophotometry (264 nm). PZQ solubility in triple distilled water was 0.33 mg/mL. The solubility range was comprised between 0.31 mg/mL and 2.51 mg/mL, values corresponding to stabilizer solution of pure P188 (0.25%) and the binary mixture HPMC-SLS (1%), respectively. Six samples (pure P188 or in binary mixtures with PVP, MD and P80) showed no significant differences with the PZQ solubility in water. In contrast, other five samples showed highly significant differences in solubility values with respect to water, where HMPC and SLS were responsible for this behavior.In conclusion, the selection of 1% (w/v) as PZQ concentration for nanosuspension development is a very conservative value to ensure supersaturation conditions.