Formulation and Evaluation of Naringenin Nanosuspensions for Bioavailability Enhancement

Abstract

The clinical potential of naringenin (NRG) is compromised due to its poor aqueous solubility and low oral bioavailability. The study is aimed at addressing these issues by means of naringenin nanosuspensions (NRG-NS) formulated using polyvinylpyrrolidone (PVP K-90) as stabiliser via antisolvent sonoprecipitation method. Optimisation of sonication time, drug concentration and stabilisers was done based on particle size. Characterisation of pure NRG and NRG-NS was carried out by scanning electron microscopy, differential scanning calorimetry (DSC), x-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). In vitro dissolution, intestinal absorption by non-everted rat intestinal sac model and in situ single pass intestinal perfusion techniques were performed for further investigation. Nanosuspensions prepared using PVP K-90 lead to minimum particle size (117 ± 5 nm) with zeta potential of -14.6 ± 5.6 mV. The particle size was affected by increasing sonication time, concentration of stabiliser and drug. Nanosizing process converted the crystalline drug into amorphous form as predicted from DSC and XRD patterns. FTIR demonstrated the formation of hydrogen bonds between drug and polymer. NRG-NS displayed a higher dissolution amount (91 ± 4.4% during 60 min) compared to NRG powder (42 ± 0.41%). The apparent and effective permeability of NRG-NS was increased as compared to the pure NRG. The in vivo pharmacokinetics demonstrated that the C and AUC values of NRG-NS were approximately 2- and 1.8-fold superior than the pure drug. Hence, overall results confirmed nanosuspensions as promising approach for NRG delivery with high absorption in gastrointestinal tract, improved dissolution and oral bioavailability.

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

“…The apparent and effective permeability of naringenin nanosuspension was increased as compared to the pure naringenin. The in vivo naringenin nanosuspension treatment showed maximum concentration and area under curve (0-24 h) values approximately 2-fold superior than the pure drug [268]. The flavonoid fisetin-loaded polymeric nanoparticles had protected and preserved the release of flavonoid fisetin in gastric and intestinal conditions.…”

“…Quercetin [267] Naringenin [268] Fisetin [269] SNEDDS Naringenin [270] Quercetin [271] Rutin [272,273] Liposomal Quercetin [274,275] Rutin [274] Kaempferol [275] Luteolin [275]…”

Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

“…Zhang et al [94] aimed to improve the oral absorption of baicalin, which has low solubility and poor permeability, by using a micellar formulation comprised of the carriers Pluronic P123 copolymer and sodium taurocholate. Sustained release profile of baicalin-loaded mixed micelles, in in vitro drug release experiment, held in several pH conditions, showed 14% drug released after 2 h in gastric conditions and 54% release within 48 h in intestinal conditions, compared to 34% and 79% release [105], nanoparticles [106][107][108][109][110], phytosome [111], nanoliposome [112], mixed micelles [113,114], SNEDDS [115,116], nanocarrier [117,118], nanoemulsion [119], nanosuspension [ Mixed micelles [129,130], nanoparticles [131,132], solid dispersion [133,134] , SNEDDS [135] , SMEDDS [136], lipid carrier [137], copolymeric micelles [138], exosomes [139] Naringenin DENV, HCV SNEDDS [140], solid dispersion [141], nanoparticles [142,143] , liposome [144], nanosuspension [145,146] In vitro uptake studies, carried out with a caco-2 cell line, determined the absorption of baicalin within the mixed micelles and verified their internalization ability. Baicalin-loaded ST-P123-MMs formulation achieved high oral bioavailability (Fig.…”

Formulation and Characterization of Lafutidine Nanosuspension for Oral Drug Delivery System

“…However, further increase in the stirring speed led to increasing in the particle size (p>0.05)of nanosuspension during precipitation method that resulted in non-uniform formulations with visible settling due to the aggregation of particles, this could be due to mechanical agitation and non-uniform mixing producing local regions of supersaturation during anti-solvent precipitation [33].…”