Loading...
3 results
Search Results
Now showing 1 - 3 of 3
- Risperidone release from solid lipid nanoparticles (SLN): validated HPLC method and modelling kinetic profilePublication . Silva, Ana Catarina; Lopes, Carla Martins; Fonseca, J.; Soares, M.E.; Santos, D.; Souto, Eliana B.; Ferreira, D.A simple reverse-phase (RP) high performance liquid chromatography (HPLC) method was developed and validated, according to the International Harmonisation Guidelines (ICH), for the determination of risperidone (RISP) from solid lipid nanoparticles (SLN). Chromatographic runs were performed on a RP-C18 column, using an isocratic mobile phase of methanol, acetate buffer (0.05 M; pH 4.6) and triethylamine (60:40:0.02, v/v/v). The flow rate was 1 ml/min, the run time was 10 min and the RISP absorbance was measured at 280 nm, using UV detection. A linear response was obtained for a RISP concentration range of 0.25 - 10.00 g/ml (R2 = 0.9996), with a detection and quantification limits of 0.011 and 0.034 g/ml, respectively. The method was shown to be specific, precise at the intra-day (RSD < 0.796%) and inter-day (RSD < 0.331%) levels, and accurate with recoveries between 86.86 - 100.3% (RSD < 0.613%). Method robustness was observed as well. The suitability of the method for RISP quantifications was assessed by the determination of encapsulation parameters (encapsulation efficiency and drug loading) and by studying the RISP release profile from SLN. Kinetic models (zero order, Higuchi, Korsmeyer-Peppas and Baker-Lonsdale) were used to fit the obtained release profile and to predict the in vivo performance of RISP-loaded SLN. A combined pattern of diffusion and erosion release mechanism (anomalous non-Fickian transport) was found for the RISP-loaded SLN, which shows the ability of the system for controlled drug release.
- Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): High pressure homogenization versus ultrasoundPublication . Silva, Ana Catarina; González-Mira, E.; García, M.L.; Egea, M.A.; Fonseca, J.; Silva, R.; Santos, D.; Souto, Eliana B.; Ferreira, D.The suitability of solid lipid nanoparticles (SLN) for the encapsulation of risperidone (RISP), an antipsychotic lipophilic drug, was assessed for oral administration. The hot high pressure homogenization (HPH) and the ultrasound (US) technique were used as production methods for SLN. All the studies on the SLN formulations were done in parallel, in order to compare the results and conclude about the advantages and limitations of both techniques. The particle sizes were in the nanometer range for all prepared SLN formulations and the zeta potential absolute values were high, predicting good long-term stability. Optical analyses demonstrated the achievement of stable colloidal dispersions. Physicochemical characterization of dispersions and bulk lipids, performed by differential scanning calorimetry (DSC) and X-ray assays, support prediction of occurrence of drug incorporation in the SLN and good long term stability of the systems. The toxicity of SLN with Caco-2 cells and the existence of contaminations derived from the production equipments were assessed by the (4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. The results showed 90% of cell viability after SLN exposure, with no significant differences within all prepared formulations (p > 0.05). From this study, we conclude that SLN can be considered as efficient carriers for RISP encapsulation. Moreover, HPH and US revealed to be both effective methods for SLN production.
- Improving oral absorption of samon calcitonin by trimyristin lipid nanoparticlesPublication . Martins, S.; Silva, Ana Catarina; Ferreira, D.C.; Souto, Eliana B.Solid lipid nanoparticles (SLN) composed of trimyristin (solid lipid) and poloxamer 407 (surfactant) were prepared by a w/o/w emulsion technique for the incorporation of Salmon calcitonin, and further explored as protein carriers for oral delivery. Trimyristin SLN showed a mean size diameter of 200 nm with an association efficiency for calcitonin of approx. 86%. The morphology of SLN was investigated by cryo-SEM and by AFM, revealing spheroid shape SLN with a smooth surface. The in vitro release of calcitonin occurred for a period of 8 h, under both gastric and intestinal simulated pH conditions, predicting suitable properties for oral administration. The pharmacological activity of the protein was evaluated following oral dosage of calcitonin-loaded SLN in rats. SLN lowered the basal blood calcium levels by up to 20% with 500 IU/kg dose sustaining hypocalcaemia over 8 h. The results indicate that incorporation of Salmon calcitonin into trimyristin SLN is a key factor for the improvement of the efficiency of such carriers for oral delivery of proteins.