Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate.

Tamoxifen Citrate (TC) is an estrogen receptor antagonist and drug of choice for hormone sensitive breast cancer. Solid Lipid Nanoparticles loaded with TC were prepared by High Shear Homogenization followed by Ultrasonication. The aim of the present work is to study the effect of four different Solid Lipids and three Surfactants on Formulation and Stability of SLN. They were characterized for Particle size, Polydispersity Index and Zeta Potential by Zetasizer Nano. SLN prepared by Solid Lipid Compritol 888 (Glyceryldibehenate) and Tween 80 (1%) showed desired Particle Size of 206.9 nm, PDI of 0.046 and Zeta Potential of 9.32 mV.

Tamoxifen Citrate (TC) is an estrogen receptor antagonist which is known to be a drug of choice for hormone sensitive breast cancer. The Solid Lipid Nanoparticles are submicron colloidal carriers (50-100 nm) which are composed of physiological lipid, dispersed in water or in aqueous surfactant solution. SLN will carry the adequate dose of the drug at the tumor site by Passive Targeting through EPR effect (Enhanced Permeability and Retention). The aim of present work is to study the effect of different types of Lipids, types of Surfactants and various concentrations of Surfactants on the Formulation and Stability of Solid Lipid Nanoparticles by characterizing SLN for Particle Size, Polydispersity Index and Zeta Potential.

Materials and Methods

Tamoxifen Citrate (TC) was received as Gratis Sample from Sun Pharma Pvt. Ltd., Vadodara. All lipids Compritol 888 (Glyceryl dibehenate), Precirol ATO 5 (Glyceryl disterate), Gelucire 50/13 Pellets (Stearoyl macrogol-32 glycerides), Galeol pellets (Glyceryl Monosterate) were kindly gifted by Gattefosse Pvt. Ltd., France. Surfactants like Lipoid S 75-3, Lipoid S PC-3, Phospholipon 80 H and Phospholipon 90 was kindly gifted by Lipoid AG, Germany.

TC loaded Solid Lipid Nanoparticles were prepared by High Shear Homogenization followed by Ultra sonication.[1] Lipid phase containing TC and the aqueous phase were heated to 70°C, separately. The aqueous phase was poured into the lipid phase, with the stirring speed of 28,000 rpm for 10 minutes with heating using Programmable Digital Homogenizer - PDH (Omni, USA). Dispersion was ultrasonicated for 10 minutes to reduce the particle size and to avoid agglomeration of particles in the dispersion. Batch was kept at 4°C for 1 day. Quantity of TC was kept 0.1%. While Drug: Lipid Ratio was kept 1:10 in the whole dispersion. 1% and 2% concentrations of Surfactant were employed to prepare various batches of SLNs.

Particle size (PS), Particle size Distribution-Polydispersity Index (PDI) and Zeta Potential of various batches were evaluated by Zetasizer Nano ZS 90 (Malvern Instruments Ltd.).

Results and Discussions

Effect of type of Lipid and concentration of Surfactants are elaborated in Tables 1 to 3. Batch No. CMPT.1 (Compritol 888 and 1% of Tween 80) was found to be stable after 30 days according to PS and PDI analysis.

Table 1

Effect of types of lipid and concentration of Tween 80 on formulation

Table 3

Effect of types of lipid and concentration of PVA on formulation

Conclusion

TC loaded SLN prepared by High Shear Homogenization followed by Ultra sonication by using Compritol 888 and Tween 80 (1%) showed good Particle size, Particle size distribution – Polydispersity Index and physical stability.

Table 2

Effect of types of lipid and concentration of Pluronic F-68 on formulation