Enhancing Delivery Technologies for Nutraceuticals

By J.W. Wong, K.H. Yuen and David Ho

In recent years, nutraceuticals have established themselves as part of the daily diet of consumers all over the world. Among the many reasons for their popularity and wide acceptance is the availability of extensive scientific research establishing their therapeutic claims, as well as the innovations involved in nutraceutical product development, including the design and development of delivery methods and technology.

Delivery technology employed in nutraceutical products is not just limited to ensuring ease of administration and convenience; but also, more importantly, to ensure good oral absorption/bioavailability, an important determinant of efficacy. Not all nutraceuticals, including those from natural products, are well absorbed upon oral administration. Studies have shown many of these molecules are inherently poorly bioavailable. For example, actives from botanicals such as Eurycoma longifolia J. (Tongkat ali), Andrographis paniculata and Orthosiphon stamineus have been shown to possess poor oral bioavailability. It is also well known that absorption of oil-soluble vitamins (A, D, E and K) is food dependent; they are poorly absorbed in the fasted state. Typical examples are the tocotrienols, which are members of the vitamin E family. The absolute oral bioavailability of alpha-tocotrienol was found to be approximately 27.7 percent, while that of delta- and gamma-tocotrienols was even lower, being 9.1 percent and 8.5 percent, respectively.

Formulating nutraceuticals with a specialized delivery technology is a promising approach to address poor oral bioavailability of lipophilic compounds. Various inventive technologies are now available, including advanced lipid-base formulations such as the self-emulsifying system (SES). An SES is a mixture of oil and surfactant, sometimes including co-solvents, that emulsifies spontaneously or under conditions of gentle agitation upon contact with an aqueous medium. It can be encapsulated in soft or hard gelatin capsules for easy administration. Upon oral administration, the content of the capsule will be liberated and self-emulsification will be initiated by digestive motility of the stomach and small intestine. An SES system available commercially is the patented Suprabio® system. It is employed for the oral delivery of tocotrienols, and is able to increase the oral bioavailability of delta-, gamma- and alpha-tocotrienols by 2.6, 2.9 and 3.0 fold, respectively, compared to a conventional oil formulation. The Suprabio SES system has also been used to significantly increase the absorption of coenzyme Q10 (CoQ10) and testosterone. Formulation aspects such as the choice and amount of oily vehicle and emulsifiers used, and optimization of the droplet size of the emulsion are crucial for the success of an SES in improving the absorption of nutraceuticals. Other lipid-base formulation includes conventional emulsion systems, multiple emulsions, multilayer emulsions and the newer cochleate delivery system, which consists of stable phospholipid-cation precipitates especially suited for labile compounds.

Another approach to improve the oral bioavailability of nutraceuticals is based on solubilization technology, whereby water-insoluble or partly soluble nutraceuticals are brought into aqueous solution through various techniques. The solubilization techniques employed can range from micellar solubilization, cosolvency, salting in, complexation and hydrotropy. Hydrotrophy is a process whereby addition of a large amount of second solute results in an increase in the aqueous solubility of another solute. This technique has been used in the Ubisol-Aqua® developed by Zymes LLC. Water-insoluble substances can form a non-covalently bound complex with Ubisol-Aqua, which leads to self-assembly into micellar arrays, leading to solubilization. Another example of micellar solubilization technique that has been applied commercially is NovaSOL® by AQUANOVA.

Many natural compounds including nutraceuticals have poor oral bioavailability. Delivering them with well-designed systems can enhance their oral bioavailability and efficacy. In this regard, consumers must be made aware of the differences among products from the standpoint of their oral bioavailability. They can then have the choice of selecting the products that are well formulated and efficacious.

Jia-Woei Wong, Ph.D., is the R&D manager at Hovid Research Sdn Bhd. Kah-Hay Yuen, B. Pharm (Hons), Ph.D., is a professor at Universiti Sains Malaysia. David Ho is the managing director of Hovid Bhd, Carotech Bhd, Bio-Fertilizer Sdn Bhd and Hovid Research Sdn Bhd.