Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

Abstract

Abstract. Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a Bcombo^approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-toaqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z ), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A=0.04, D/L=0.03, and Tw20=2.50%w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0±0.9 nm, ζ-potential of −24.2±1.2 mV, and DL and EE of 2.9±0.1 and 97.6±0.1%w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.

Study on influence of polymer and surfactant on in vitro performance of biodegradable aqueous-core nanocapsules of tenofovirdisoproxil fumarate by response surface methodology

“…This might be attributed to the ability of surfactant to reduce the interfacial tension and hence the interfacial free energy, so that higher amount of surfactant results to an emulsion with high interfacial area, that means smaller particle size with good stability (Sinko, 2017). The results were in agreement with those reported by Rehfeld in case of benzene-in-water emulsions (Rehfeld, 1967); and also with those reported by Gupta et al(2015) in case of solid lipid nanoparticles (Gupta et al, 2015). The particle size was found to be influenced by the type of polymer as bigger size particles were observed with PLGA RG503H followed by PLA R203H and smaller size particles were observed with PLGA RG502H.…”

Untitled

“…Therefore, higher amount of surfactant results an emulsion with smaller particle size and good stability. These results related to those reported by Rehfeld [29] for benzene-in-water emulsions; and also with those reported by Gupta et al [30] for solid lipid nanoparticles. The particle size of ACNs prepared with PLGA RG503H was found to be high, and it was decreased in the order of PLA R203H and PLGA RG502H.…”

Ultrahigh verapamil-loaded controlled release polymeric beads using superamphiphobic substrate: D-optimal statistical design, in vitro and in vivo performance

“…Similar results were obtained while formulating different multiparticulate systems (Patel et al, 2006;Piyakulawat et al,. 2007;Mobarak et al, 2014;Gupta et al, 2016). In this study, VP and the polymers were completely soluble in methylene chloride and fast solidification of the beads occurred due to the high volatility of the solvent.…”