Raloxifene-loaded SLNs with enhanced biopharmaceutical potential: QbD-steered development, in vitro evaluation, in vivo pharmacokinetics, and IVIVC.

摘要: Raloxifene hydrochloride, a second-generation selective estrogen receptor modulator, has been approved for the management of breast cancer. However, it is known to exhibit poor (~ 2%) and inconsistent oral bioavailability in humans, primarily ascribable its low aqueous solubility, extensive first-pass metabolism, P-gp efflux, presystemic glucuronide conjugation. The present research work entails systematic development evaluation SLNs RLX enhanced biopharmaceutical performance against Factor screening studies were conducted using Taguchi design, followed by optimization employing Box-Behnken design. Preparation was carried out glyceryl monostearate Compritol® 888 ATO (i.e., lipid), Phospholipid S-100 co-surfactant), TPGS-1000 surfactant) solvent diffusion method. optimized formulation evaluated zeta potential, average particle size, field emission scanning electron microscope, transmission microscopy, vitro release study. Further, MCF-7 cells (cell cytotoxicity assay, apoptosis reactive oxygen species assay) Caco-2 uptake efflux employed evaluate anticancer potential developed formulation. In vivo pharmacokinetic Sprague-Dawley rats therapeutic profile SLN formulations exhibited mean size 109.7 nm, PDI 0.289 with - 13.7 mV. drug dissolution showed Fickian release, exponent 0.137. Cell cellular indicated 6.40-, 5.40-, 3.18-fold improvement efficacy RLX-SLNs vis-a-vis pure RLX. Besides, quite significantly improved drug, 4.06-fold Cmax, 4.40-fold AUC(0-72 h), 4.56-fold AUC(0-∞), 1.53-fold Ka, 2.12-fold t1/2, 1.22-fold Tmax. high degree level A linear correlation established between fractions dissolved (in vitro) absorbed vivo) at corresponding time-points. Stability robustness when stored 3 months. Results obtained from different construe promising RLX-SLNs, thereby ratifying lipidic nanocarriers as an efficient delivery strategy improving attributes