Investigation Of Solid Lipid Nanoparticles Loaded With Diclofenac Sodium

Solid lipid nanoparticles (SLNs) are novel colloidal carriers for controlled drug delivery system. SLNs combine the advantages of polymeric nanoparticles and o/w fat emulsions for drug delivery administration, such as a good tolerability, protection of incorporated active compounds against chemical degradation, a high bioavailability by oral administration, large-scale production by high pressure homogenization. SLNs are usually applicable for entrapping lipophilic drugs. However, for hydrophilic drugs, they are shortcomings with lower drug entrapment efficiency (EE) due to their limited solubility in lipid matrix.The aim of this study was to assess various formulation and process parameters to enhance the incorporation of a water-soluble drug (diclofenac sodium, DS) into SLNs prepared by emulsion/solvent evaporation method. The lipid materials ( with or without phospholipid) was one of the most important factors that determine the character and drug loading of the system. The type of surfactant could also change the EE and drug loading (DL). Results also showed that the EE of DS was increased to approximately 100% by lowering the pH of dispersed phase. The EE of DS-loaded SLNs (DS-SLNs) had been improved by the existence of cosurfactants and the increase of PVA concentration. Stabilizers and their combination with PEG 400 in the dispersed phase also resulted in higher EE and DL. EE increased and DL decreased as the phospholipid/DS ratio became greater, while the amount of DS had an opposite effect. In addition, it was concluded that EE and DL of DS-SLNs were not affected by either the stirring speed or the viscosity of aqueous and dispersed phase.According to the investigations, drug solubility in dispersion medium played the most important role in improving EE.Improving the liposolubility of water-soluble drugs is an attractive way to enhance their loading efficiency as long as hydrophobic lipid carriers are concerned. Some efforts have been made to increase their affinity to ydrophobic carrier materials by chemical modification of such drugs. However, this process has always accompanied with the irreversible denaturation of active compounds. An alternative choice based on hydrophobic ion pairing has been proposed to improve the liposolubility of some proteins. Unfortunately, this method is limited to the alkaline peptides with high isoelectric points (PI). In a previous report, Cui et al. and their group have developed a novel solvent evaporation method to prepare polymeric nanoparticles loaded with insulin-phospholipid complex which had successfully improved the solubility of the insulin and enhanced the EE. However, the novel phospholipid complexes (PCs) emulsion/solvent evaporation strategy employed to produce SLNs loaded with hydrophilic drugs has not been reported so far.SLNs loaded with DS–phospholipid complexes (PCs) were prepared by a modified emulsion/solvent evaporation method, in which phospholipid was adapted to improve the liposolubility of DS. Both the solubility and partition coefficient study were employed to detect the liposolubility of DS in PCs. FT-IR spectra analysis were also used to confirm the formation of PCs. The effects of PCs on the morphology, particle size, surface charge and encapsulated drug of the SLNs were also investigated. DS could be solubilized effectively in the organic solvent with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies (EE) could be obtained with the addition of PCs. Furthermore, according to the TEM observation, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which suggested that phospholipid formed multilayers around the solid lipid core of SLNs. FT-IR spectra and DSC were also used to confirm the formation of SLNs. In conclusion, the model hydrophilic drug-DS can be successfully formulated into the SLNs with the help of PCs which also modified all the aspects of SLNs.