Adding a new chapter to the history of capsule-based drug delivery

By Kevin Robinson | Published: 10-Jul-2023

For more than 100 years, capsules have consisted of two pieces (a body and a cap). Nutritional or pharmaceutical ingredients are dosed into the body and the cap is then placed over the mouth and snapped shut. Now, however, next-generation technology is bringing a new dimension to this popular oral solid dosage form

Dr Kevin Robinson (KSR) recently caught up with Tobie Louw (TL), Vice President of Operations at Vantage Nutrition (An ACG Group Company), to discuss the market introduction of a new dietary supplement format called “Sidebysides”, brought about by the invention of the world’s first three-piece capsule, and to discover how they came to be.

“The oral capsule has for more than 100 hundred years been the most effective and efficient way to bring the widest range of fixed-dose oral health solutions to market. There continues to be significant new investment in its ongoing evolution to assist with human health endeavours.  This is the latest chapter in its rich history,” says Tobie.

“Sidebysides” are the world’s first side by side separated oral dose health products for nutraceuticals and pharmaceuticals,” he says, “that have been created by the invention of a new three-piece capsule.”

The third piece is the inventive introduction of a cup-shaped divider membrane inside a standard off-the-shelf capsule — made from the same material as the capsule — that acts as a divider inside the body of the capsule."

"This enables wet and dry ingredients or incompatible actives to be housed side by side — together but separate in one product. “Sidebyside dietary supplements are rapidly gathering momentum since being launched in a vegetarian capsule format in 2020,” he adds.

ComboCap, the technology-based start-up that invented and commercialised Sidebyside technology and products during the past 10 years, has developed and received 80 international patent awards for Sidebysides.

The company designed, optimised and produced the unique Sidebyside technology and manufacturing process as well as the machines used to currently produce Sidebyside dietary supplements exclusively in their own world-first Sidebyside plant in New Jersey, US. ACG acquired ComboCap in early 2023.

ACG is known for its enabling innovation and technology in the dietary supplement and pharmaceutical spaces. 

Discussing the manufacturing process, Tobie explains that a completely new type of encapsulation machine technology and process is used to produce Sidebyside products. “A Sidebyside machine takes an empty off-the-shelf hard capsule, removes the cap, doses the liquid and then inserts and seals the membrane into place. The cap is then replaced,” he says. 

“In the second stage of the process, the powder encapsulation takes place; the cap is removed, the powder dosed and the cap put back on — completing a Sidebyside product. This innovative technology is being extended to enable multiphase dosing on one single Sidebyside machine.”

Adding a new chapter to the history of capsule-based drug delivery

Groundbreaking technology
Key benefits for the greater life sciences industries include the fact that the three-piece Sidebyside form factor maximises the dose volumes on both sides of the membrane. It also enables customised dose sizes because the membrane position within the capsule is movable. Transparent capsules are used so that the contents of both chambers are fully visible.

“The Sidebyside product format provides an ideal way to combine generally sensitive ingredients, such as probiotics, with other incompatible nutrients and actives,” adds Tobie.

The dual-phase capsule-in-a-capsule has, of course, existed in the market for some time. In a cap-in-cap, a small capsule containing a powder dose is placed inside a larger one containing a liquid dose. This form factor results in the outer liquid capsule and dose being dissolved before the inner powder capsule and dose are.  

“With Sidebysides, the capsule shell of both chambers dissolve at the same time, enabling the ingredients to disperse and work together simultaneously; this delivers benefits such as the better absorption of key nutrients in the presence of oils.”

The future rollout programme for Sidebyside products includes a number of features that cover the delayed release of the whole capsule and the release of the two independent chambers at different stages.

“Delayed release is relevant because there is a significant market demand for health products that dissolve later in the digestive tract, or require a dual-stage instant beneficial effect followed by a gradual sustained one. An example of the latter is an oral health product that assists with falling asleep followed by staying asleep,” notes Tobie.  

KSR: What is the movable membrane and what is its function?  
TL:
The membrane acts as a barrier between the two ingredients. It can be located in the optimum position, allowing the manufacturer to size the doses and the chambers accordingly — such as when one of the two ingredients requires a larger dose than the other.

KSR: How do Sidebyside products differ from capsule-in-capsule products?
TL:
With Sidebysides, the separate ingredients operate together after ingestion; the chambers dissolve together. With cap-in-cap products, the separated ingredients dissolve sequentially. There are application needs for the sequential dissolution dynamic, especially when the inner chamber is required for late release.

The Sidebyside product format and technology can however enable both parallel or sequential release, and can discharge either chamber ahead of the other depending on the need. 

Often, Sidebyside products can help to solve incompatibilities; examples include when ingredients haven’t previously been able to be combined or in the general case of needing to pair liquid and powder nutrients.

By housing them with a dividing membrane, it’s possible to retain the identity and efficiency of the separated doses that may otherwise have been compromised if they had been combined and started reacting together sooner. This plays a role in enhanced product stability and shelf-life.

When it comes to capsule-in-capsule products, the outer oil protects the inner capsule after ingestion and the powder is thereafter released for digestion. The oil helps to function as a delayed release solution. With Sidebysides, the use of clear capsules brings an added benefit in that a consumer has full side by side visibility of both separated ingredients in the capsule.

This transparency can help to enhance patient trust ion the product and co-use buy-in and compliance. Product communication and marketing is also facilitated when references can be made to the separated contents.

KSR: Can you expand on some of the enhanced combinations and what they can achieve? 
TL:
Sidebyside products launched by brand companies to date have covered the following applications: general vitality, immunity, prenatal, woman’s health, men’s health, thyroid, sleep, calm, weight management and others.

Select pharmaceutical Sidebyside applications are also being considered. One example is VASCEPA (icosapent ethyl) a pharmaceutical-grade fish oil. Published research by Amarin shows that VASCEPA DHA, when co-used with statins, brings patients a substantial enhancement in the benefits of the statin.

Bringing a single two-in-one Sidebyside “VASVEPA-STAT” product to market would ensure co-use and give the combination solution in a more convenient single product format. 

KSR: Where next for this technology? 
TL:
We are currently exploring a number of exciting controlled released options. This includes bringing single-stage, two-stage and triple-delayed release Sidebysides to market.

Triple-delayed release Sidebysides can utilise a number of ingredient formats including liquids, powders and beadlets, whereby a mix of delayed-release beadlets is used to achieve the second and third stage release after the early stage release of the liquid dose.

We are also progressing the development of beadlet-liquid and powder-powder and liquid-liquid Sidebyside health products. To date, no commercially available separated powder-powder oral health dose product exists in the market … and they have not been possible in existing capsule formats.

In addition, we’re looking at developing the science behind exciting combinations such as prebiotic/probiotic Sidebysides in powder-powder form. 

By continuing to invest, extend, and bring to market the latest, most effective and efficient capsule technologies and innovative oral-dose health products, ACG continues to build its lead innovator status as a global top tier capsule company.


 

 

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