Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: physicochemical characterization and in vivo investigation

Figures & data

Figure 1 Solubility of fenofibrate in aqueous solutions of various hydrophilic carriers.

Notes: Each value denotes the mean ± SD (n=3): (A) 1% (w/v) polymers and (B) 1% (w/v) surfactants.

Abbreviations: PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin; SD, standard deviation; HPC, hydroxypropyl cellulose; PVA, polyvinyl alcohol; HPMC, hydroxypropyl methylcellulose; CMC, carboxymethylcellulose; PEG, polyethylene glycol.

Figure 2 Effect of various nanoparticulated formulations on the aqueous solubility of fenofibrate.

Notes: Each value represents the mean ± SD (n=3): (a) fenofibrate powder, (b) PVP nanospheres, (c) HP-β-CD nanocorpuscles, and (d) gelatin nanocapsules. P<0.05 for each formulation compared to the drug powder.

Abbreviations: SD, standard deviation; PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin.

Figure 3 Effect of various nanoparticulated formulations on the dissolution of fenofibrate.

Notes: Each value shows the mean ± SD (n=6): (a) fenofibrate powder, (b) PVP nanospheres, (c) HP-β-CD nanocorpuscles, and (d) gelatin nanocapsules. P<0.05 for each formulation compared to the drug powder.

Abbreviations: SD, standard deviation; PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin.

Figure 4 Solid state characterization.

Notes: (A) PXRD patterns, (B) DSC thermograms, and (C) FTIR spectrograms: (a) fenofibrate powder, (b) PVP nanospheres, (c) HP-β-CD nanocorpuscles, and (d) gelatin nanocapsules.

Abbreviations: PXRD, powder X-ray diffraction; DSC, differential scanning calorimetry; FTIR, Fourier-transform infrared; PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin.

Figure 5 Scanning electron micrographs.

Notes: (A) Fenofibrate powder (×2,000), (B) PVP nanospheres (×20,000), (C) HP-β-CD nanocorpuscles (×20,000), and (D) gelatin nanocapsules (×20,000).

Abbreviations: PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin.

Table 1 Pharmacokinetic parameters

Parameter	Fenofibrate powder	PVP nanospheres	HP-β-CD nanocorpuscles	Gelatin nanocapsules
AUC (h μg/mL)	17.72±1.52	61.01±14.66*	42.59±11.55*	96.80±15.42*,#
Cmax (μg/mL)	2.36±0.34	6.73±1.75*	6.46±1.83*	9.14±2.47*
Tmax (hours)	1.58±0.20	2.67±1.03	1.25±0.27*	1.75±0.27
t1/2 (hours)	6.08±0.92	6.70±0.28	5.29±0.78	6.17±0.58
Kel (hour^−1)	0.12±0.02	0.10±0.004	0.13±0.02	0.11±0.01
MRT (hours)	7.41±0.50	7.95±0.08	6.65±0.31	7.91±0.21

Notes: Each value indicates the mean ± SD (n=6).

* P<0.05 compared with fenofibrate powder.

# P<0.05 compared with other nanoparticulated formulations.

Abbreviations: PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin; SD, standard deviation; AUC, area under the curve; t_1/2, half-life; K_el, elimination rate constant; MRT, mean residence time.

Figure 6 Mean plasma level–time profiles of fenofibric acid in rats after the oral administration of various formulations.

Notes: (a) Fenofibrate powder, (b) PVP nanospheres, (c) HP-β-CD nanocorpuscles, and (d) gelatin nanocapsules. Each dose was equivalent to 20 mg/kg fenofibrate. Each value designates the mean ± SD (n=6). At all of the time points, each fenofibrate-loaded nanoparticulated formulation showed P<0.05 compared to the drug powder. *P<0.05 for gelatin nanocapsules compared with the other formulations.

Abbreviations: PVP, polyvinylpyrrolidone; HP-β-CD, hydroxypropyl-β-cyclodextrin; SD, standard deviation.