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. 2016 Jun 14:11:2829-38.
doi: 10.2147/IJN.S104187. eCollection 2016.

Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug

Kazi Mohsin  1 , Rayan Alamri  1 , Ajaz Ahmad  2 , Mohammad Raish  3 , Fars K Alanazi  1 , Muhammad Delwar Hussain  4
Affiliations

Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug

Kazi Mohsin et al. Int J Nanomedicine. .

Abstract

Background: Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate.

Materials and methods: LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat.

Results: The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient SNEDDS as they had higher solubility of the drug and produced nanosized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain >98% drug in solution for >24 hours in aqueous media. The in vivo pharmacokinetics parameters of SNEDDS formulation in comparison with pure drug showed significant increase in C max and AUC0- t , ~78% and 67%, respectively. The oral BA of fenofibrate from SNEDDS in rats was ~1.7-fold enhanced as compared with the BA from pure drug.

Conclusion: Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product for administering the poorly water-soluble drug, fenofibrate, with an enhanced oral BA.

Keywords: fenofibrate; lipid-based formulation; oral bioavailability; self-nanoemulsifying drug delivery systems; solubility improvement.

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Figures

Figure 1
Figure 1
Chemical structure of fenofibrate.
Figure 2
Figure 2
The effect of nonionic surfactants on the particle size of lipid-based nano-formulations. Notes: Miglyol 812 (medium chain triglyceride) and Imwitor 988 (medium chain mono- and diglycerides) at fixed ratio (7:3 w/w) were used with different surfactants. Data are expressed as mean ± SD, n=3.
Figure 3
Figure 3
Effect of dilution with water (pH 6.0), 0.1 M HCl (pH 1.1), and phosphate-buffered saline (PBS; pH 7.5) on the solubility of fenofibrate in formulation F5, Type IIIB (I308/HCO30 50/50, % w/w). Note: Data are expressed as mean ± SD, n=3.
Figure 4
Figure 4
The percentage of fenofibrate precipitated during 24 hours after 1:100 dilution in the dissolution medium (fenofibrate was dissolved at 80% of the equilibrium solubility in the anhydrous mixture). Notes: The formulations represent F1 – M812:I988(7:3)/TO-106V (1/1), F2 – M812:I988(7:3)/HCO30 (1/1), F3 – M812:I988(7:3)/CrEL (1/1), F4 – M812:I988(7:3)/CrRH40 (1/1), F5 – I308/HCO30 (1/1), F6 – I308/CrEL (1/1), and F7 – I308/CrRH40 (1/1). Data are presented as mean ± SD, n=3.
Figure 5
Figure 5
Plasma concentration–time profiles of fenofibrate after a single oral administration of fenofibrate SNEDDS formulation, M812:I988(7:3)/TO-106V (1/1), and fenofibrate powder (FF) to rats at a dose equivalent to 9 mg/kg fenofibrate (mean ± SEM, n=6). Abbreviations: SEM, standard error of mean; conc, concentration; SNEDDS, self-nanoemulsifying drug delivery systems.
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