Several strategies can be employed to improve poor oral bioavailability: enhancement of aqueous solubility, protection against gastrointestinal degradation, increase in intestinal permeability, inhibition of intestinal metabolism and P-glycoprotein mediated efflux, use of delivery systems to facilitate intestinal absorption (1, 2).
Micronisation and, to a higher extent, nanonisation improve the aqueous solubility/dispersion and consequently intestinal absorption and bioavailability. Encapsulation of plant-derived products into cyclodextrins enhances both the aqueous solubility and stability. Chitosan-based delivery systems afford gastric stability, enhanced penetration through intestinal membrane and protection against intestinal metabolism. Another approach to improve the oral bioavailability of lipophilic products, especially of those undergoing extensive liver first pass metabolism, is to increase the rate of their intestinal lymphatic uptake. This can be achieved by using lipid-based delivery systems such as nanoparticles and liposomes. A major cause of poor oral bioavailability is the extensive enzymatic metabolism in the intestinal epithelial cells. P-Glycoprotein is another factor limiting oral bioavailability. Being highly expressed in the intestinal epithelium, P-glycoprotein pumps the absorbed compounds back into the intestinal lumen thus reducing their absorption rate. Co-administration of metabolic enzyme and P-glycoprotein inhibitors are important strategies for oral bioavailability enhancement. P-Glycoprotein inhibition can be also achieved by using dendrimers as carriers. Dendrimers, usually used for encapsulation of poorly water soluble products, inhibit P-glycoprotein by endocytosis (1, 2).
Nanosized delivery systems significantly improve oral bioavailability. Solid lipid nanoparticles provide prolonged gastric retention, controlled release and site specific drug delivery. Self-emulsifying drug delivery systems improve oral bioavailability of lipophilic products while polymer-based nanoparticles are used to protect and deliver the hydrophilic ones (1, 3).
Phytosomes, molecular complexes between plant-derived products and phosphatidylcholine (1:1 or 2:1), have high loading capacity and chemical stability affording significant increases (3-6 fold) in oral bioavailability (1, 3).
To conclude, limited oral bioavailability of plant-derived products can be successfully overcome by selecting a proper formulation strategy. There are many strategies to improve oral bioavailability. The selection of the best one is challenging and should rely on the chemical and pharmacokinetic properties of herbal constituents. In addition, the delivery system selection is of great importance as it significantly influences the delivery efficiency.
1. Ting Y, Jiang Y, Ho C-T, Huang Q. (2014). Common delivery systems for enhancing in vivo bioavailability and biological efficacy of nutraceuticals. Journal of Functional Foods, 7, 112-128.
2. Hetal T., Bindesh P., Sneha T. (2010). A review on techniques for oral bioavailability enhancement of drugs. International Journal of Pharmaceutical Sciences Review and Research, 4 (3), 203-222.
3. Bilia A. R., Isacchi B., Righeschi C., Guccione C., Bergonzi M. C. (2014). Flavonoids loaded in nanocarriers: an opportunity to increase oral bioavailability and bioefficacy. Food and Nutrition Sciences, 5, 1212-1227.