Nanostructured lipid nanocarrier scaffold of ranolazine: preparation, optimization, in vitro and in vivo evaluations.

Abstract

The present study aimed to develop and optimise Ranolazine-loaded Nanostructured Lipid Carriers (RNZ-NLCs) to overcome the poor oral bioavailability and rapid clearance associated with Ranolazine, thereby improving its therapeutic efficacy. RNZ-NLCs were prepared using the hot high-pressure homogenisation technique and optimised using a 2³ factorial design. Characterisation techniques included dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infra-red spectroscopy (FTIR), in vitro drug release profiling, and pharmacokinetic analysis in rats. The optimised RNZ-NLCs exhibited a mean diameter of 205.8 nm, a polydispersity index (PDI) of 0.318, a surface charge (Zeta potential) of -22.4 mV and drug loading of 8.01% w/w. DSC and XRD studies confirmed the transformation of Ranolazine into an amorphous state, and FTIR indicated no chemical interaction with excipients. In vitro release studies showed a sustained release profile, with 65% drug release at 12 hours and 90% at 24 hours, fitting the Korsmeyer-Peppas model. Long-term storage stability studies over 90 days revealed no significant changes in particle characteristics. Pharmacokinetic evaluation in rats showed that RNZ-NLCs increased the Cmax to 18.621 µg/mL (from 9.413 µg/mL for free RNZ), delayed Tmax to 4 h (from 2 h), and enhanced AUC₀-∞ to 217.02 µg·h/mL (from 32.06 µg·h/mL). Additionally, mean residence time (MRT) and elimination half-life (t₁/₂) were extended to 11.83 h and 6.81 h, respectively. RNZ-NLCs significantly improved the pharmacokinetic profile and storage stability of Ranolazine, indicating their potential as a promising delivery system for enhancing oral bioavailability and therapeutic efficacy.