Formulation, Optimization and In vivo Evaluation of Freeze-Dried Nanocapsules for Enhancing the Oral Delivery of...

This study aims to develop the freeze-dried core-shell nanoparticles (nanocapsules; NCs) as an effective dosage form for improving the therapeutic activity of valsartan (VAL). NCs were created employing the nanoprecipitation process and optimized using a 3² full factorial design to estimate the effect of the oily core and the polymeric shell concentrations on the particle size (PS), entrapment efficiency (EE), and % release efficiency after 4 h (RE_4h). The optimized NCs exhibited a PS of 50.37 ± 6.39 nm, a PDI of 0.120 ± 0.016, a ZP of -63.7 ± 1.7 mV, an EE of 89.83 ± 1.49%, and a RE_4h of 48.32 ± 2.35%, while displaying a spherical morphology with a transparent coating membrane under TEM. Furthermore, lyophilization with 5% w/v mannitol developed a porous powder that exhibited the ideal required features (EE of 88.49 ± 1.75%, PS of 104.8 ± 4.38 nm, PDI < 0.25). FT-IR analysis revealed the compatibility of valsartan with the used excipients, while DSC and XRD demonstrated the drug's transformation to an amorphous state upon dispersion in the nanocapsular matrix. Additionally, the lyophilized formulation substantially improved VAL's dissolution rate and showed superior stability at different storage temperatures. In vivo studies demonstrated a rapid antihypertensive effect of the lyophilized VAL-loaded NCs within 15 min and a 2.71-fold increase in oral bioavailability compared to the pure valsartan suspension, emphasizing the potential of these generated carriers for the efficient oral delivery of VAL and the control of hypertension.