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. 2020 May 31;10(6):1085.
doi: 10.3390/nano10061085.

Oral Bioavailability Enhancement of Raloxifene with Nanostructured Lipid Carriers

Aditya Murthy  1   2 , Punna Rao Ravi  2 , Himanshu Kathuria  2   3 , Shrinivas Malekar  2
Affiliations

Oral Bioavailability Enhancement of Raloxifene with Nanostructured Lipid Carriers

Aditya Murthy et al. Nanomaterials (Basel). .

Abstract

Raloxifene hydrochloride (RLX) shows poor bioavailability (<2%), high inter-patient variability and extensive gut metabolism (>90%). The objective of this study was to develop nanostructured lipid carriers (NLCs) for RLX to enhance its bioavailability. The NLC formulations were produced with glyceryl tribehenate and oleic acid. The particle characteristics, entrapment efficiency (EE), differential scanning calorimetry (DSC), in vitro drug release, oral bioavailability (in rats) and stability studies were performed. The optimized nanoparticles were 120 ± 3 nm in size with positive zeta potential (14.4 ± 0.5 mV); % EE was over 90% with the drug loading of 5%. The RLX exists in an amorphous form in the lipid matrix. The optimized RLX-NLC formulation showed sustained release in vitro. The RLX-NLC significantly (p < 0.05) enhanced oral bioavailability 3.19-fold as compared to RLX-free suspension in female Wistar rats. The RLX-NLC can potentially enhance the oral bioavailability of RLX. It can also improve the storage stability.

Keywords: bioavailability; glyceryl behenate; nanostructured lipid carriers; osteoporosis; raloxifene; solid lipid nanoparticle.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of surfactant concentration on particle characteristics (d-avg, PDI, zeta potential) and percentage of entrapment efficiency (% EE).
Figure 2
Figure 2
Effect of the amount of oleic acid (% w/w) on the NLC particle characteristics (d-avg, zeta potential and PDI).
Figure 3
Figure 3
Effect of the P407 concentration on the percentage cumulative release of RLX from the NLCs.
Figure 4
Figure 4
Differential scanning calorimetry (DSC) thermograms of the physical mixture of ingredients used in the NLCs. GB: glyceryl behenate; RLX: raloxifene hydrochloride.
Figure 5
Figure 5
Pharmacokinetic profile of RLX for 24 h after oral administration of the optimized NLC formulation (NLC 3) and the RLX suspension in female Wistar rats. Data are given as the mean ± SD (n = 3).
Figure 6
Figure 6
Stability of the particles as a function of time at 4 °C. (A) Particle size as the Z-average, polydispersity index (PDI) and zeta potential. (B) Particle sizes of d50, d90, d95.
Figure 7
Figure 7
Stability of the particle as a function of time at room temperature. (A) Particle sizes as the Z-average, PDI and zeta potential. (B) Particle sizes of d50, d90, d95.
Figure 8
Figure 8
Shelf-life estimation of the RLX-solid lipid nanoparticles (SLNs) (A) at 4 °C and (B) at 25 °C ± 2 °C and 60% ± 5% RH. Dotted line shows the 95% confidence interval limits.
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