Self-Microemulsifying Drug Delivery System of Phillygenin: Formulation Development, Characterization and Pharmacokinetic Evaluation

Abstract

Phillygenin, as an active ingredient of Forsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin.

Enhanced oral bioavailability and anti‐hyperuricemic activity of liquiritin via a self‐nanoemulsifying drug delivery system

“…The TEM image (Fig. 2(B)) shows that the LQ‐SNEDDS was regular sphere with good dispersibility, which agrees with Wang's result 19 . The EE and DL of LQ‐SNEDDS were respectively 91.32% ± 2.39% and 2.44% ± 0.04%, and the result indicated that a large amount of LQ was encapsulated in SNEDDS.…”

Application of Design of Experiments in the Development of Self-Microemulsifying Drug Delivery Systems

“…Another CCD strategy was used by Yan and coworkers to examine the similar responses (droplet size, PDI, and dissolution efficiency) toward SMEDDS for β-elemene formulation composing poly (acrylic acid) (PAA) entailed on mesoporous silica nanoparticles (MSNPs). The authors emphasized the use of the PAA/MSNPs loaded in SMEDDS to increase the drug loading and to act as the pH triggers in improving a controlled release behavior in an acidic environment [ 82 ]. Several reports of CCD applications that have been incorporated in SMEDDS are listed in Table 6 .…”

Approaches to Improve bioavailability and oral absorption of low water-soluble drug by self- emulsifying drug delivery system

“…Due to the short length of the carbon chain, MCTs directly diffuse through the gastrointestinal tract by the mechanism of passive diffusion into the portal system without undergo any molecular modifications. Lipids enable faster absorption from of the gastrointestinal tract compared to long-chain triglycerides and are preferred due to their greater capacity for drug dissolution and higher resistance to oxidation [16,17]. Triglyceride vegetable oils are well absorbed and digested.…”