Innovations in Liquid Supplement Formulations and Delivery

by Jeff Taylor

The health and nutrition industry often looks to technological innovations in sports nutrition for novel formulation solutions to specific ingredient challenges. Liquid technologies in supplement form are one of the ways performance-based sports nutrition has moved the needle in innovation. Part of the challenge of creating liquid or lipid-based formulations is to provide a means of optimizing delivery while maintaining stability. Here are four examples of formulation innovations from sports nutrition designed to do just that:

Coenzyme Q10 (CoQ10) is a critical nutrient involved in the production of energy within cells. An endogenous cellular constituent present in the mitochondria, it is a mediator of electron transport and energy production.¹ It also is a co-antioxidant with vitamins E and C because it maintains both vitamins in their reduced state.² CoQ10s antioxidant activity can offer preventive benefits to heart conditions,^3,4,5,6 angina,^7,8,9 blood pressure modulation^10,11,12 and immunity.^13,14

CoQ10 is a powder with almost no solubility in water and a melting point of 48° to 50°C. This means absorption is low. To overcome the issue, many formulators have increased the amount of CoQ10 per dose; but, an innovative solution is to use a self-emulsifying delivery system to increase solubility and bioavailability instead. That is done using a liquid natural emulsifier and other natural solvents previously shown to improve the gut absorption of compounds with low-water solubility.

In a clinical test, this formulation was compared to the bioavailability of three different commercially available formulationseffervescent tablets, powder in hard gelatin capsule, and a liquid dispersion in a soft gelatin capsule.¹⁵ Twenty four volunteers were given a single dose of 60 mg of CoQ10 in a randomized, single-dose, four-way crossover study, with a seven-day washout period. Plasma levels of CoQ10 following administration with the liquid capsule formulation indicated a 30-percent higher in vivo bioavailability relative to the other three. The study concluded the better bioavailability of the Licaps® capsule CoQ10 formula was due to its complete dissolution in a lipid matrix based on lecithin and vegetable oils that enhance permeation for poorly soluble products.

Resveratrol is found in the skin of red grapes and in red wine. Scientists hypothesize that resveratrol activates an enzyme, SIRT1, in the cell. SIRT1 produces fresh mitochondria, a key component of cells that generates power in muscles and other tissues. The presence of new mitochondria burns sugar more slowly to release energywhich in turn enhances endurance and boosts the metabolic rate.¹⁶

The resveratrol molecule is prone to degradation if exposed to oxygen, heat or light. By using a liquid-filled, hard gelatin capsule that is flushed with nitrogen before it is fused shut, the oxidative action can be reduced while protecting the contents from light through an opaque shell. Stability data collected over time proves this is an excellent strategy for stabilizing resveratrol.¹⁷

Astaxanthin has been called the king of carotenoids because it is the most powerful of this class of antioxidants, offering 10 times the antioxidant activity of other carotenoids. It is a colorful fat- or oil-soluble pigment, found in microalgae, salmon, trout, krill, shrimp and the feathers of some birds such as flamingos. Studies indicate astaxanthin might benefit the immune, cardiovascular and central nervous systems, as well as enhance endurance and speed recovery time after strenuous exercise.¹⁸

Because it is a fat-soluble, unstable phytochemical, astaxanthin is optimally delivered in a liquid form. Dissolved in a lipid carrier and encapsulated under a nitrogen blanket, it can be more stable and more highly bioavailable than other delivery forms. An in vitro CaC0₂ study showed a significant difference between the permeability of a liquid encapsulated formulation and a tablet formulation.¹⁹

L-arginine is a building block of protein. It is a precursor of nitric oxide (NO), which causes blood vessel relaxation for a positive cardiovascular effect. Because it stimulates protein synthesis, arginine has been studied for body building; combined with weight lifting and a hyper-caloric diet, it helps promote weight management by reducing body fat and increasing lean mass.²⁰

In a liquid form, an L-arginine suspension has been micronized and solubilized into a clear, free-flowing liquid with a high concentration of the ingredient. Particle size has been reduced from 100 micrometers down to 177 nanometersmore than 1,000 times reduction in size. The dissolution and improvement in particle size were designed to boost bioavailability. Furthermore, encapsulating this liquid formula in a hard-shell capsule in a nitrogen-flushed environment has been shown to maintain the stability of this product compared to other forms of L-arginine.²¹

Formulators tools help the industry improve delivery and improve use of dietary supplement ingredients.

Jeff Taylor is the new product development manager at Capsugel , Greenville, SC.

Innovations in Liquid Supplement Formulations and Delivery References

1. Cooper JM, Schapira AH. Friedreich's Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy. Biofactors. 2003;18(1-4):163-71.

2. Crane FL, Navas P. The diversity of Coenzyme Q 10 function. Mol Aspects Med. 1997;18(Suppl):S1-S6.

3. Weber C et al. Antioxidative effect of dietary coenzyme Q10 in human blood plasma. Int J Vit Nutr Res. 1994;64:311-15.

4. Mortensen SA et al. Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure. Drug Exp Clin Res. 1985;11:581-93.

5. Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 in patients with congestive heart failure: a long-term multicenter randomized study. Clin Invest. 1993;71:S134-36.

6. Berman M et al. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin Cardiol. 2004 May;27(5):295-9. Comment in: Clin Cardiol. 2004 Oct;27(10):A26; author reply A26, A30.

7. Fujioka T, Sakamoto Y, Mimura G. Clinical study of cardiac arrhythmias using a 24-hour continuous electrocardiographic recorder (5th report)antiarrhythmic action of coenzyme Q10 in diabetics. Tohoku J Exp Med. 1983;141(Suppl):453-63.

8. Kamikawa T et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol. 1985;56:247.

9. Mortensen SA. Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone). Clin Invest. 1993;71:S116-23.

10. Gaby AR. The role of coenzyme Q10 in clinical medicine: part II. Cardiovascular disease, hypertension, diabetes mellitus and infertility. Alt Med Rev. 1996;1:168-75.

11. Hodgson JM, Watts GF. Can coenzyme Q10 improve vascular function and blood pressure? Potential for effective therapeutic reduction in vascular oxidative stress. Biofactors. 2003;18(1-4):129-36.

12. Hodgson JM et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr. 2002 Nov;56(11):1137-42. 

13. Folkers K et al. Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Comm Pathol Pharmacol. 1982;38:335-38.

14. Lockwood K et al. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Comm. 1995;212:172-77.

15. Capsugel, data on file.

16. So Whats the Scoop on That Stuff in Red Wine Thats Supposed to Let You Live Forever? by David Stipp, Fortune, February 5, 2007, p. 72 and 76-77.

17. Capsugel, data on file.

18. Natural Astaxanthin:  King of the Carotenoids. By Bob Capelli with Gerald R. Cysewiski, Ph.D. (Cyanotech Corp., 2007).

19. Capsugel, data on file.

20. Arginine for Sports and Fitness, Popular Supplements for Sports and Fitness.  www.naturesbounty.com/vf/healthnotes/HN_live/benefits_Sports/Arginine.htm

21. Capsugel, data on file.