Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

Abstract

Background: A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs. Methods: The microemulsion formulation was optimized using a pseudoternary phase diagram, comprising propylene glycol dicaprylocaprate (PG), Cremophor ® RH40, and water (30/46/24 w/w). Results: The microemulsion increased the oral bioavailability of hydroxysafflor yellow A which was highly water-soluble but very poorly permeable. The relative bioavailability of hydroxysafflor yellow A microemulsion was about 1937% compared with a control solution in bile duct-nonligated rats. However, the microemulsion showed lower enhanced absorption ability in bile duct-ligated rats, and the relative bioavailability was only 181%. In vitro experiments were further employed to study the mechanism of the enhanced effect of the microemulsion. In vitro lipolysis showed that the microemulsion was digested very quickly by pancreatic lipase. About 60% of the microemulsion was digested within 1 hour. Furthermore, the particle size of the microemulsion after digestion was very small (53.3 nm) and the digested microemulsion had high physical stability. An everted gut sac model demonstrated that cumulative transport of the digested microemulsion was significantly higher than that of the diluted microemulsion. Conclusion: These results suggested that digestion of the microemulsion by pancreatic lipase plays an important role in enhancing oral bioavailability of water-soluble drugs.

Nanoemulsion-based delivery system for enhanced oral bioavailability and Caco-2 cell monolayers permeability of berberine hydrochloride

“…In recent years, nanoemulsions has become a promising approach for the delivery of poorly water-soluble drugs to improve oral bioavailability as well as to modify drug release characteristics (Aboalnaja et al, 2016;Akhtar et al, 2016;Khani et al, 2016). The mechanisms for enhanced absorption of nanoemulsions are very complex, involving improved solubility of drug molecules, formation of mixed micelles, opening of tight junctions, and improved lymphatic delivery (Qi et al, 2011;Aboalnaja et al, 2016). The aim of this study was to develop a nanoemulsion delivery system of BBH to improve its stability, oral bioavailability, and to evaluate its in vitro membrane permeability using Caco-2 cell model (Balimane et al, 2004;Piazzini et al, 2017 All other chemicals were of the analytic grade.…”

Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach

“…First, the W/O-ME could be transformed into an O/W or W/O/W emulsion after it is diluted, and both of these types of emulsions can increase cell membrane fluidity, thus improving the permeability of drug molecules. 40 Cheng et al reported a W/O-ME formulation for the oral delivery of earthworm fibrinolytic enzyme, demonstrating that the W/O/W emulsion might be a primary converted formulation that improves the stability of the earthworm fibrinolytic enzyme in harsh gastric fluid and intestinal juices when the W/O-ME was administered orally. 41 Second, the high oil content of the W/O-ME (35.65%) used in the present study may lead to an increase in the lymphatic transport of the drug relative to that with the O/W-ME (2.10%).…”

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

“…23,32 Second, the synergistic effect of oil phase and surfactants in the ME could increase cell membrane fluidity and open the tight junctions between cells to enhance the drug absorption. 24,51 As already mentioned, the largest AUC among three pharmaceutical techniques was obtained in GMME, mostly due to its unique absorption pathway. Therefore, it is very important to choose an appropriate technique that will improve drug solubility and bioavailability.…”