Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation

Abstract

Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT14) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT14) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT14) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.

Formulation, characterization, in vitro and in vivo evaluations of self-nanoemulsifying drug delivery system of luteolin

“…There are few studies that have reported DPPH scavenging activity of luteolin better (IC 50 ≈ 2 µg/ml) than ascorbic acid (IC 50 ≈ 6 µg/ml) and tocopherol (IC 50 ≈ 10 µg/ml) [94]. Similarly, in another report, the DPPH scavenging activity of luteolin was found better (IC 50 = 1.8 µM, that is equivalent to about 0.5 µg/ml) than vitamin E, α-tocopherol (IC 50 = 5.2 µM) [95]. Despite the slightly different IC 50 of luteolin-loaded SNEDD from that of pure luteolin, the differences between DPPH scavenging activities at all tested concentration levels were not statistically significant.…”

Enhancing Solubility and Bioavailability of Artemether and Lumefantrine through a Self-nano Emulsifying Drug Delivery System

“…Oil-in-Water (O/W) nano emulsions will be spontaneously formed when SNEDDS is exposed to GI fluids. The physicochemical properties of drugs encapsulated in nano emulsions significantly change and overcome the multiple bio-barriers in GI tract leading to improved oral bioavailability [9][10][11][12] .…”

Self-Nanoemulsifying Drug Delivery Systems for Enhancing Solubility, Permeability, and Bioavailability of Sesamin

“…As a lipid-based drug formulation, SNEDDS has advantages such as thermodynamic stability, shelf stability, and high drug entrapment [14]. Triglycerides were also part of the composition of SNEDDS because they could easily form chylomicrons and pass through the lymphatic system [31]. Upon oral administration, the SNEDDS undergoes a self-emulsifying process in gastrointestinal fluids and forms o/w micelle droplets with a size of <100 nm [32], which are easy to disperse and promote a component distribution.…”

“…As a lipid-based drug formulation, SNEDDS has advantages such as thermodynamic stability, shelf stability, and high drug entrapment [14]. Triglycerides were also part of the composition of SNEDDS because they could easily form chylomicrons and pass through the lymphatic system [31].…”