Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug☆

Hanafy, Abeer; Spahn‐Langguth, Hildegard; Vergnault, Guy; Grenier, P.; Grozdanis, M Tubic; Lenhardt, T.; Langguth, Peter

doi:10.1016/j.addr.2007.04.005

Cited by 184 publications

(73 citation statements)

References 12 publications

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“…The lipid nanocarriers (SLNs) merely increased oral bioavailability of FN by 24.34%-89.05% relative to two micronized FN suspensions (dispersed in hydroxethyl cellulose solution or sirupus, respectively). 17 The particle size of drug and formulation composition are not the ultimate determinants to transepithelial absorption of BCS II drugs. The in vivo fates of nanoparticles most likely also play a key role in oral drug absorption.…”

Section: Introductionmentioning

confidence: 99%

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Zhang¹,

Chen²,

Zhang³

et al. 2014

IJN

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Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl ® ), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.

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Section: Introductionmentioning

confidence: 99%

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Zhang¹,

Chen²,

Zhang³

et al. 2014

IJN

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“…Moreover, the particle size can influence the speed of particle diffusion through the mucous layer to reach intestinal epithelial cells. 37,38 In addition, the nanosuspensions have inherent advantages in enhancing oral absorption. First, nanoparticles exhibit high bioadhesion to the intestinal wall that can prolong the retention time in the gastrointestinal tract and increase passive absorption.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

Qiao

Chen

Rui

et al. 2017

IJN

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Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d -α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability ( P app ) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS ( P <0.01). Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in C max and area under the curve of plasma concentration versus time from zero to the last sampling time (AUC 0− t ) ( P <0.01). An evaluation of the anti-inflammatory effect on Carr-induced paw edema demonstrated that the ADG-NS were more effective in reducing the rate of paw swelling, producing a greater increase in the serum levels of nitric oxide (NO), Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) ( P <0.01) and an increase in superoxide dismutase activity ( P <0.05) compared to the ADG coarse powder. This study indicated that nanosuspensions could act as an effective delivery device for ADG to enhance its oral bioavailability and biological efficacy.

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“…45 The plasma concentration-time profiles of fenofibric acid after the oral administration of untreated fenofibrate or ALC formulation are illustrated in Figure 9. The pharmacokinetic parameters are summarized in Table 2.…”

Section: In Vivo Pharmacokineticsmentioning

confidence: 99%

Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

Yang

Shao

Han

2016

IJN

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This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC). The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w), krill oil to fenofibrate of 2:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration ( C max ) and area under the curve (AUC) of fenofibric acid (an active metabolite) in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate.

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Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug☆

Cited by 184 publications

References 12 publications

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

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Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug☆

Cited by 184 publications

References 12 publications

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-&alpha;-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

Aminoclay&ndash;lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

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Product

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Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption