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

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 AUC 0– 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.

Evaluation of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water-Soluble Talinolol: Preparation, in vitro and in vivo Assessment

“…This result is consistent with the previous reports (Mohsin et al, 2016). The decrease in the droplet size might be the result of more surfactant being available to stabilize the oil-water interface.…”

“…The enhanced oral bioavailability of TAL may also be due to the faster uptake of the nanoemulsion resulting from SNEDDS formulation by enterocytes at the absorption site (Elgart et al, 2013). There are several reports which confirm this view (Zhang et al, 2014, 2015; Mohsin et al, 2016).…”

“…The decrease in the droplet size might be the result of more surfactant being available to stabilize the oil-water interface. It is more likely with SNEDDS formulations that the larger the surface area, the faster and complete are the absorption rate of drugs (Mohsin et al, 2016). Furthermore, the decrease in the droplet size represents the formation of a unique close-packed surfactant film at the oil-water interface (Table 2), there by stabilizing the oil droplets (Gershanik and Benita, 2000; Pouton, 2000).…”

“…Solubility and dissolution is primarily the rate limiting factors for oral bioavailability of many drugs. There have been a variety of formulation strategies designed over the past two decades to improve drug solubility to enhance the rate and extent of drug absorption from the GIT (Shahba et al, 2012, 2016, 2017; Devraj et al, 2013; Mohsin et al, 2016).…”

Role of Alternative Lipid Excipients in the Design of Self-Nanoemulsifying Formulations for Fenofibrate: Characterization, in vitro Dispersion, Digestion and ex vivo Gut Permeation Studies

“…In comparison to many other drug delivery systems, SNEDDS can maintain drug in solution for considerable amount of time prior to absorption, increase intestinal absorption ( Ibrahim et al, 2014 ) and have the potential to reduce the extent of efflux and pre-systemic metabolism. These effects can enhance the bioavailability and provide the desired reproducible pharmacokinetic profile of orally administered drugs such as fenofibrate ( Mohsin et al, 2016 ).…”