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The evolving demand for delivery innovations.jpg

The evolving demand for delivery innovations

Increasing bioavailability in supplements can improve health and quality of life outcomes for patients, be a better use of resources from an ecological perspective and yield better results from a business perspective.

Most drugs and nutrients are administered orally to increase patient compliance and enable distribution and packaging. This requires absorption in the gastrointestinal tract, and distribution throughout the body until they reach the relevant target site. Pharmaceutical companies have used drug or nutrient delivery systems (DDS) for many years, and the dietary supplements industry is now catching up. DDS has the capacity to facilitate increased nutrient absorption, while at the same time reducing or eliminating the effect of food on the absorption of these now bioactive compounds.1,2

Although nutritional ingredients can be very effective at addressing various health concerns, the doses required are usually high, involve a high frequency (i.e., three times a day), and have a long onset of action. All of these are mainly due to poor (or low) absorption (bioavailability). Many people suffer from “pill fatigue,” which leads to poor compliance., and This results in poor health outcomes.

Improvement in bioavailability can lead to improved efficacy, faster onset of action, lower doses and improved user compliance; this, in turn, can lead to improved health and quality of life outcomes for patients, better use of resources from an ecological perspective, and better results from a business perspective.

FDA’s Biopharmaceutics Classification System (BCS) has been used to classify and predict the bioavailability of pharmaceuticals since 2000.3,4 It can also be applied to nutraceutical ingredients. Four major classes define the BCS, and the drugs are classified based on three significant factors governing bioavailability, namely, dissolution, solubility and permeability. According to BCS the drug substances are classified as shown:

Table 1. Biopharmaceutical Classification System (BCS)

Class

Solubility

Permeability

Example

I

High

High

Leucine

II

Low

High

CoQ10, tocopherol, creatine monohydrate

III

High

Low

Catechin

IV

Low

Low

Curcumin, quercetin

Consumer demand

For consumers, the bioavailability of a nutrient or bioactive compound is literally how well, or how much is absorbed by the body. Technically speaking, the oral bioavailability of a nutraceutical is the amount of the ingested nutrient that reaches the blood still in an active form. This is very important, as only those nutrients that are bioavailable can be distributed to the tissues or organs where they can exert a real health benefit.

Traditional formats such as tablets, hard capsules and soft gel capsules still dominate the mainstream dietary supplements industry, but this is changing. “Pill fatigue,” results in poor compliance, and a demand for lower doses (smaller capsules), or novel formats.

Convenience is key for consumers in both active nutrition and nutraceuticals. Easy to take formats in active nutrition are growing. This category began with ready-to-mix (RTM) protein powders, and new ingredients still need to be used in this way. This had led to consumer demand for ingredients that can dissolve or disperse in water. Until recently, actives such as curcumin or resveratrol couldn’t mix in water, as they would only agglomerate (form a gluggy mess.) Due to the same hydrophobicity (water-hating) properties, these and other lipophilics (fat-loving) such as coenzyme Q10 could not be used in effervescent tablets or powders, limiting that format to vitamin B and other hydrophilic ingredients.

New technologies in nutraceuticals

There are many emerging technologies or adaptations of pharmaceutical delivery systems now being adopted in nutraceuticals and active nutrition. The best in the market support their claims with:

  • Formulation development (bioavailability performance and formulation stability)
  • Pharmacokinetics (human blood plasma draw studies)
  • Mechanistic studies
  • Clinical studies

Coenzyme Q10 is widely used for cardiovascular health, in sports nutrition for energy and endurance, and as an antioxidant. It is also well known to be poorly absorbed. Ironically, when prescribed for cardiovascular health it is directed to be taken with a fatty meal.

In September 2019, an Australian study was published highlighting a three-fold increase in the absorption of ubiquinone (CoQ10).5 It also demonstrated that the use of the delivery system helped the ubiquinone to match that of ubiquinol for absorption.

For many years, ubiquinol has been held as the “gold standard” of CoQ10 in terms of pharmacokinetics. Of interest, this study tested three similar delivery systems, each producing different sized micelles upon self-emulsification. Usually, scientific trials don’t test multiple actives across study arms, but this trial had five arms: one CoQ10 control, one ubiquinol, and three CoQ10 delivery systems. The results showed a linear trend in relation to the particle size produced upon emulsification (i.e., absorption or its measure [AUC] increases as particle size decreases). This emphasizes the importance of specifying the micelle (particle) size and volume distribution when attributing improvements of bioavailability with formulations. The delivery system also negated the “food effect.”

Omega-3 polyunsaturated fatty acids are well known and provide many health benefits, including improved cardiovascular, cognitive, joint, eye and skin health, reduced inflammation, and improved psychological outcomes. Like ubiquinone, optimal omega-3 absorption is achieved with a high-fat meal as a result of the digestion process, stimulating the release of bile salts and digestive enzymes.

The same self-emulsifying technology as the ubiquinone study (a customized formulation for ethyl ester fish oil) was tested to show superior enhancement in the absorption and bioavailability of omega-3s.6 The single-dose pharmacokinetic study was designed with participants on a low-fat diet,  because the National Cholesterol Education Program (NCEP) recommends that patients with hypertriglyceridemia consume meals with very low-fat content (<15% fat content).7 The report concluded the delivery system provided enhanced oral bioavailability (six times) of omega-3s without the requirement of a fatty meal through improved digestion and long-chain fatty acid absorption.

Dispersion, rather than emulsification of solid particles (powders), is a more recent development. In this regard, the nutraceuticals industry is outpacing the pharmaceutical industry. This delivery technology provides two impressive benefits.

  • Firstly, high bioavailability, due to the increased specific surface area of lipophilic particles that haven’t agglomerated. This has been demonstrated in trials run on ingredients such as curcumin,8 resveratrol, palmitoylethanolamide and Boswellia. As the ingredients remain as powders, this allows use in dosage formats such as ready-to-mix powders or effervescents.
  • Secondly, the format delivers 90% active ingredient (using only 10% excipient or delivery system). This industry-leading ratio allows smaller or fewer doses, as well as ease of incorporation into multi-active formulations.

The most widely recognized material using this technology was investigated in a pharmacokinetic study published in the European Journal of Nutrition in 2018.8 This material has also been validated by a mechanistic study undertaken by Professor Clive Prestidge’s research group at the School of Pharmacy and Medical Science at the University of South Australia, which focuses on drug formulation and delivery.9

Nutrient delivery is essential: making medicines and nutrients easier to take, reducing dosages, and improving compliance leads to improved health outcomes and better sales.

Eric is the co-founder of Pharmako Biotechnologies Pty. Ltd. With over 18 years’ experience in the nutraceuticals industry, he has specialized in bringing to market innovation from both a product and material perspective. Eric has senior sales and marketing expertise with a strong commercial background, with extensive experience in business with FMCG, wholesale, retail and the B2B supply chain.

References

1 Kuentz M. “Lipid-based formulations for oral delivery of lipophilic drugs.” Drug Discov Today Technol. 2012;9(2):e71-e174

2 Yohei Kawabata et al. “Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications.” Int J Pharm. 2011;420:1-10.

3. Oehlke K et al. “Potential bioavailability enhancement of bioactive compounds using food-grade engineered nanomaterials: a review of the existing evidence.” Food Funct  2014;5:1341.

4 Ranade V et al. “Oral Drug Delivery.” Drug Delivery Systems 3rd edition CRC Press, 2011;215-242.

5 Briske D et al. “The impact of micelle size and increased absorption of ubiquinone using a novel delivery system (AquaCelle).” Int J Pharmacokinet. 2019;doi:10.4155.

6 Bremmell K et al. (2019) “A self‐emulsifying Omega‐3 ethyl ester formulation (AquaCelle) significantly improves eicosapentaenoic and docosahexaenoic acid bioavailability in healthy adults.” Eur J Nutr. 2019;doi:10.1007.

7 Eilat-Adar S et al. ”Nutritional recommendations for cardiovascular disease prevention.” Nutrients. 2013;5(9):3646-3683.

8 Briskey et al. “Increased bioavailability of curcumin using a novel dispersion technology system (LipiSperse).” Eur J Nutr. 2019;58(5):2087-2097.

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