Preparation and characterization of solid lipid nanoparticles of furosemide using quality by design

Abstract

ABSTRACTThe present work aimed to synthesize solid lipid nanoparticles (SLNs) of Furosemide (FRSM). The parameter sensitivity analysis showed a significant effect of particle size and reference solubility on the AUC0–∞, Cmax and tmax. The FRSM-encapsulated SLNs were synthesized by the phase inversion temperature (PIT) technique using 32 factorial design. The optimal level of 221.28 mg of Compritol 888 ATO and 420 mg of Cremophor RH 40 showed a mean hydrodynamic diameter (MHD) of 25.54 ± 0.57 nm, a polydispersity index (PdI) of 0.158 ± 0.01, the % entrapment efficiency of 80.70 ± 4.06%, percent dissolution efficiency of 71.72 ± 1.52% and time elapsed for 50% drug release of 3.67 ± 0.15 h. The PIT was determined using the turbidity method and the values ranged between 75°C and 73°C. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) images represent spherical to sub-spherical and smooth surface of SLN. The Fourier transform-infrared (FTIR), differential scanning calorimetry (DSC) and x-ray diffraction (XRD) depict the drug-excipient compatibility. Korsmeyer–Peppas was found to be the best fit release kinetics model (R2 = 0.973; K-value = 29.96 and release exponent = 0.40), predicting the Fickian diffusion. The results advocate that the optimized formulation (OF) could promote the controlled release, and improve the physicochemical stability of the formulation. Hence, SLN could be a potential drug carrier for the peroral delivery of FRSM.