Dietary control - the rate release route

Dr Michelle Jones from ADM discusses the controlled delivery technology in nutraceutical applications

ADM has recently introduced a CDT system for its nutraceutical ingredient, Novasoy soya isoflavone concentrate, to produce a product range called Novasoy Daily. Here, the science behind CDT is reviewed, its comparative benefits discussed and the article highlights how ADM has successfully applied this technology. Dietary supplements are now widely used by consumers to complement a healthy balanced diet. However, in a highly competitive marketplace, key points of differentiation can be obtained by using the latest technology to produce ingredients that offer consumers dietary supplements that have improved efficiency and convenience.

One recent development in dietary supplement ingredient manufacture is controlled delivery technology or CDT, developed by Scolr Inc, a US company with expertise in nutraceuticals and the development of innovative controlled release systems. Scolr has applied materials science, colloid chemistry and biopharmaceutics to develop monolithic matrix systems collectively referred to as 'self-correcting matrix delivery systems'. These systems control the release of a precise quantity of active ingredient over a pre-determined time frame.

geometric modifications

Scolr has developed a platform of patented technologies that can be applied to compounds with a wide range of properties and characteristics¹. CDT is based upon a simple hydrophilic swellable matrix model, but it incorporates a number of geometrical modifications. It uses in-situ ionic associations between the active compound and the ionic excipients to control the diffusion of a precise quantity of either single or multiple active ingredients from the supplement product over a pre-determined time.

The formulated tablet hydrates upon contact with fluid in the stomach. Hydrophilic polymers and excipients react with the available 'water of hydration', forming a gel layer around the tablet core and creating a 'closed' microenvironment.

Selected excipients control the rate of hydration, allowing a gel matrix to form and control the active's release around the microenvironment of the tablet core. Ionic, anionic and amphoteric excipients maintain the integrity of the gel region, thereby preventing the collapse of the dissolution channels formed by the hydration of swellable polymers. These materials facilitate the phenomena of 'salting in' and 'salting out' of the active ingredients for controlled release (see figure 1).

Depending upon the system's composition, different release rates and patterns can be established to mimic more closely the manner in which the nutrients would be obtained from normal dietary consumption patterns of the parent foods.

CDT has the potential to change how nutraceutical ingredients for dietary supplements are developed and supplied.

By using a CDT platform, natural consumption patterns are simulated, offering an effective and convenient way to deliver the potential benefits of soya isoflavones. Greater consumer awareness of soya isoflavones has been stimulated by positive scientific research findings in areas such as maintaining well-being during mid-life, in bone health and heart health maintenance.²

similar structures

As a result, increasing numbers of consumers are looking to incorporate soya isoflavones into their day-to-day diets.

Isoflavones have a chemical structure that shares some similarities with the human hormone oestrogen and are sometimes referred to by the generic term 'phytoestrogens'. Although they are non-steroidal in character, isoflavones seem to be capable of possessing both pro-estrogenic and anti-estrogenic properties. They are found in soya beans, typically accounting for 0.027-0.1% by weight of the bean, and can also be found at very low concentrations in other food crops such as peas, beans and certain legumes.

Soya beans contain a range of isoflavones: the two most abundant are genistein and daidzein, followed by glycitein, although the total content in the bean depends on its variety and cultivation.³

intake figures

The consumption of soya and soya bean products is traditionally high in parts of East Asia: for example, in Japan the average daily intake of soya isoflavones is estimated to be in the region of 50mg per person.⁴

However, in Europe, the average intake of soya isoflavones is estimated to be as low as 1-3mg per day.⁵ To achieve isoflavone levels similar to those in Japan would require a major change in the diet of Western consumers, especially when one considers that even vegetarians in Europe consume only about 7mg isoflavones/day⁶.

Supplements have the potential to provide a useful and convenient source of isoflavones in these low soya-consuming countries. To cater for this need, soya isoflavones are now available in a wide range of dietary supplements designed to suit differing consumer requirements.

Novasoy Daily is the first ADM product to be developed and marketed using CDT. It provides a predictable and controlled release of soya isoflavones over time to give consistent availability and stable performance.

To develop the desired profiles and release times, more than 50 formulations were evaluated before a non-covalently bonded matrix system incorporating free-flowing and compression friendly GRAS excipients was selected. The colloidal chemistry phenomenon of salting out is particularly needed to moderate the swelling and erosion kinetics of the non-ionic polymer matrix containing the Novasoy soya isoflavones and one or more electrolytes.

matrix system

The formulations currently available demonstrate linear and sustained release over the chosen time period and dose range (figures 2 and 3). This is in contrast to other delayed release formats currently available, where the majority of the active ingredient is lost from the supplement within the first two hours after consumption.

Novasoy Daily is designed for ease of use with conventional tableting or hard shell capsule manufacturing equipment. The matrix system is made ready blended into a free-flowing dry mix that can be directly compressed to produce cost-effective monolithic tablets. Customised formulations are available in the form of specific pre-mixes into which the supplement manufacturer can make its own range of products by incorporating additional active ingredients.

CDT offers a number of benefits to both supplement manufacturers and their customers. These benefits include:

•Tailored delivery. Controlling the release of isoflavones from the supplement avoids the sudden burst in availability of nutrients seen in immediate release tablets and can provide the lower and more consistent isoflavone levels expected from normal food consumption patterns where several smaller soya meals would be consumed each day;

•Reliability. Reproducible release of the active ingredient is a necessary criterion for an effective release system. The CDT matrixÕs ionic excipients solubilise very predictably; a reliable release profile is therefore achieved. Consistency is also vital; the rate of release should not be adversely affected by ionic strength, pH or other conditions in the digestive tract;

•Flexibility. The ability to manufacture products with a wide range of doses in different formats is required to meet the needs of a diverse supplement market and variety of product offerings. The CDT system is not dependent on special manufacturing conditions or equipment, and it is amenable to the manufacture of both compressed tablets and hard shell capsules. The format means that production can easily be transferred from one manufacturing location to another;

•Durability. Finished dietary supplements should be robust and rugged products, requiring no special handling or packaging; products manufactured using CDT offer this durability and robustness. No harsh manufacturing processes are used, which means that there is no disruption of the active components.

For example, in the case of Novasoy Daily, the forms of the isoflavones present and their natural ratios remain unaffected by incorporation into the matrix formulation;

•Consumer compliance. Consumer acceptance of new products and technologies is a consideration for supplement manufacturers. Experience gained within the pharmaceutical industry indicates that end-users favour orally taken supplements. As dietary supplements manufactured from ingredients made with CDT are the same size as traditional tablets or capsules, they are very acceptable to consumers. Convenience is also a key requirement. CDT enables manufacturers to offer a once-daily dose, whereas immediate release formats may need to be consumed several times per day.

CDT is a key innovation in nutraceutical ingredient manufacture, delivering both dietary supplement manufacturers and consumers with a number of benefits.

Manufacturers are offered new opportunities for product development and diversification. By using ingredients produced with a patented CDT system, manufacturers can differentiate products from the competition through enhanced performance, reliability and cost-effective processing.

Meanwhile, consumers are able to benefit from the advantages of easy-to-take and highly efficient dietary supplements. In the future, it is likely that CDT will be applied to an increasing numbers of nutraceutical ingredients in dietary supplements.

Dr Michelle Jones

Dr Michelle Jones is technical manager for Europe with ADM's Natural Health and Nutrition division. A Ph.D. chemist, she joined ADM with a wealth of nutritional and technical experience gained from technical management positions and involvement with a key food industry trade association focusing on health and nutrition. In her current role she provides scientific guidance and service in this growth area of functional ingredients.