LC Evaluation of Intestinal Transport of Praziquantel

Praziquantel (PZQ) is a highly lipophilic drug with low aqueous solubility. Despite this, it is well absorbed from the gastrointestinal tract. In this study, a simple LC method was developed and validated, in order to monitor the concentration of PZQ in TC-199 buffer in vitro, in the rat everted gut sac absorption model. PZQ was analyzed by a reversed-phase LC method with an isocratic mobile phase containing acetonitrile and water in the proportions 45:55. The flow-rate was 1 mL min⁻¹ and PZQ was determined by measuring absorbance at 215 nm, at 25 °C. The method was found to be specific, as none of the components of TC-199 or intestinal sac artefacts interfered with the drug peak. Recovery was within acceptable statistical limits. The limit of detection was 0.54 μg mL⁻¹ and the limit of quantitation was 1.63 μg mL⁻¹. The calibration curve was found to be linear in the concentration range of 10–90 μg mL⁻¹ PZQ. The proposed method was found to be rapid and selective and hence can be applied in the monitoring of the absorption of PZQ in in vitro everted gut sac absorption studies.     

Loading of praziquantel in the crystal lattice of solid lipid nanoparticles

Praziquantel (PZQ) is the drug of choice for oral treatment of schistosomiasis and other fluke infections that affect humans. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. In this article, solid lipid nanoparticles loaded with PZQ (PZQ-SLN) were prepared by a modified oil-in-water microemulsion method selecting stearic acid as lipid phase after solubility screening studies. The mean particle size (Z-Ave) and zeta potential (ZP) were 500 nm and −34.0 mV, respectively. Morphology and shape of PZQ-SLN were analysed by scanning electron microscopy revealing the presence of spherical particles with smooth surface. Differential scanning calorimetry suggested that SLN comprised a less ordered arrangement of crystals and the drug was molecularly dispersed in the lipid matrix. No supercooled melts were detected. The entrapment efficiency (EE) and loading capacity of PZQ, determined by high performance liquid chromatography, were 99.06 ± 0.3 and 17.48 ± 0.05, respectively. Effective incorporation of PZQ into the particles was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure. Stability parameters of PZQ-SLN stored at room temperature (25 °C) and at 4 °C were checked by analysing Z-Ave, ZP and the EE for a period of 60 days. Results showed a relatively long-term physical stability after storage at 4 °C, without drug expulsion.     

Thermal characterization of solid lipid nanoparticles containing praziquantel

Solid lipid nanoparticles (SLNs), loaded and unloaded with praziquantel (PRZ-load SLN and PRZ-unload SLN) were prepared by two different procedures: (a) oil-in-water hot microemulsion method, obtaining at 70 °C an optically transparent blend composed of surfactant, co-surfactant, and water; and (b) oil-in-water microemulsion method, dissolving the lipid in an immiscible organic solvent, emulsified in water containing surfactants and co-surfactant, and then evaporated under reduced pressure at 50 °C. The mean diameter, polydispersity index (PdI), and zeta potential were 187 to 665 nm, 0.300 to 0.655, and −25 to −28 mV respectively, depending on the preparation method. The components, binary mixture, SLNs loaded and unloaded with PRZ, and physical mixture were evaluated by differential scanning calorimetry (DSC) and thermogravimetry (TG). The non-isothermal isoconversional Flynn-Wall–Ozawa method was used to determine the kinetic parameters associated with the thermal decomposition of the samples. The experimental data indicated a linear relationship between the apparent activation energy E and the pre-exponential factor A, also called the kinetic compensation effect (KCE), allowing us to determine the stability with respect to the preparation method. Loading with PRZ increased the thermal stability of the SLNs.