Evaluating visible liquid capsules

Nicolas Madit, head of formulation, and Dominique Cade, director of chemical research and development, discuss the advantages of using visible liquid capsules

Competition within the dietary supplements market is intense with an ever-increasing stream of new market entrants. So many products on the market mean consumers are faced with greater choice, and the key issue for supplement manufacturers, therefore, is how to differentiate their products and so gain and maintain a sustainable advantage.

When purchasing a dietary supplement, the consumer is influenced by a number of key factors: the product, packaging, dosage form and, of course, price. The following article focuses on one of these elements — the product delivery system. Reviewing consumer demand and the latest developments in capsule technology, it looks at ways in which the manufacturer can not only enhance the production process, but also deliver a product with high consumer appeal.

In February 2000, research into consumer capsule preferences in the USA indicated that the majority of consumers prefer liquid filled capsules. The nationwide survey was conducted in 14 cities to test the visible liquid capsule concept.

Participants in the survey included consumers of both sexes and all adult age groups who had recently purchased natural products, including vitamins, minerals and herbal products.

The results demonstrated consumer support for the visible liquid capsule concept; 69% of participants responded positively to purchasing liquid delivery supplements based on an unbranded product description. The research concluded that the liquid dosage form has strong appeal with herbal, vitamin and mineral users and is widely accepted across all natural product user demographics — both genders and all age groups.

In addition to being easy to swallow, consumers believed that the liquid filled capsule offers gentler and more natural absorption while also masking unpleasant tastes and odours.

the Licaps concept

Capitalising on the popularity of the liquid capsule concept among dietary supplement consumers, Capsugel has developed Licaps — a specially designed capsule that enables manufacturers to develop new liquid filled lines quickly and cost effectively.

The versatile capsules can be formulated in an oily phase and filled with a variety of materials, from herbal extracts to vitamins, in the following forms:

By filling capsules with liquids or semi-solids, highly accurate levels of weight and content uniformity can be achieved — to a variation of around 2.5%. This means that every capsule contains the amount of marker and excipient as defined in the finished product description.

formulation considerations

The decision whether to develop a complete product from start to finish or outsource certain parts of the process has a significant impact on time and cost. With this in mind, Capsugel offers several options for product development, from a standard line of capsules filled with liquids and herbal extracts through to customised formulations and contract manufacturing.

Consideration is also given to key production issues that determine the overall quality and performance of the final product such as raw material selection, shelf-life and compatibility.

By eliminating the outlay of in-house capabilities, bulk filled capsules enable manufacturers and retailers to focus on the marketing, speed to market and commercialisation of the packaged product with minimal risks and cost implications.

Capsugel's bulk filled Licaps product line comprises 33 standard product line formulations, based on 25 oil and herb raw materials. It includes leading herbal products such as saw palmetto, St. John's Wort, kava kava, ginkgo biloba, echinacea and valerian.

There are several reasons why some manufacturers require a customised formulation:

Adopting the new liquid delivery form extends product life and enhances consumer appeal.

The importance of raw material selection cannot be overlooked. Label claims can only be met if the quality of incoming raw materials can be guaranteed. Raw materials are the major influence on the cost of goods and can also have an effect on the formulation stability. By selecting reliable suppliers and materials, end-product quality can be guaranteed.

For instance, although 'ginkgo biloba' is a standardised claim, in reality, only 75% of gingko biloba supplements contain the proper ingredients. It is important to note that the cost of raw materials often reflects their purity and quality and that the highest marker content is not always the best.

For example, the leaves and branches of ginseng give extracts with higher marker content, but the ginsenosides are not those described in the USP (United States Pharmacopoeia) monograph.

The USP monograph requires that extraction is performed with only the roots of the panax meyer ginseng. So with higher potency, the manufacturer and end user may not be getting what they have paid for.

critical stability and shelf life

At present, there are no harmonised standards governing dietary supplement manufacturing practices in Europe and the USA, nor are companies required to put their supplements through such stringent approval procedures as in the pharmaceutical sector.

It is argued, therefore, that consumers have no guarantee as to the effectiveness of the product and retailers cannot be certain of the product's shelf life.

Several factors affect the stability of a product and can result in a change in physical properties over a shelf-life period. Certain actives used in dietary supplements are sensitive to moisture and may react with excipients. Likewise, certain excipients may interact with the gelatine capsule wall. For example, tablets are exposed to air and may react with moisture. The choice of material and particle size is therefore critical in maintaining physical stability.

Capsugel has developed methods of analysis for measuring the stability of health supplements, ensuring that Licaps will remain stable throughout their shelf life — namely the duration after manufacture for which the marker content conforms to the composition claim.

Stability is determined by assay of the markers extracted from the finished filled capsule formulation. The assay methods, mainly based on chromatography methods (HPLC and GC), were developed and validated at laboratories in Europe and the US.

The stability index was defined as the ratio of assay at an elapsed time, typically after three or six months storage at accelerated stability conditions, to assay at manufacture date. The tracer assay conforms when the stability index is higher than 90%. A shelf-life guidance of two years is provided for capsules that meet these specifications after storage for three months at 40°C/75% RH.

extensive studies

Capsugel has conducted an extensive study on the interaction between the fill and the capsule shell of hard capsules in which more than 300 liquids, pastes and powders were evaluated.

This has made it possible to validate a preliminary compatibility process consisting of three evaluation methods, outlined as follows.

The aim of the process is to provide customers with data that assesses the absence of interaction between their customised formulations and the hard capsule shell.

Traditionally, manufacturers have sealed the capsule and reduced the risk of leakages by banding them; that is, wrapping a thin band of gelatine round the capsule join — a difficult and costly exercise.

Licaps capsules however, are sealed using innovative Liquid Encapsulation Microspray Sealing (LEMS) technology, developed in-house, a process which is both cost-effective and more efficient.

The process consists of three stages:

1. Remoisturising: a machine sprays the gap between the capsule halves with a water and ethanol mixture. This lowers the melting temperature of the gelatine. This is shown in Figure 1.

2. Fusing: gentle heat, 40°C to 60°C, is applied to the capsule, locally melting the remoisturised zone and fusing the cap to the body without affecting the integrity of the rest of the capsule. This ensures the capsule is tightly sealed and prevents the risk of liquid leaking out of the capsule.

3. Setting: the gelatin hardens and sets as the product returns to room temperature.

protect active substances

The hard gelatine capsules used for Licaps offer a number of benefits over other capsule types including low oxygen permeability, see Figure 2.

Hard gelatine capsules protect the active substance against oxygen, as the permeability of the capsule wall to oxygen is extremely low due to the absence of plasticiser. The oxygen permeability of the capsule wall has been studied by MOCON, and the permeability to air over 24 hours was identified as follows 0.04ml — 0.05ml in the capsule cap, and 0.01ml — 0.02ml in the capsule body.

The low oxygen permeability of hard gelatine capsules allows an increased level of protection for products that are sensitive to oxygen, for example, oils.

The hard gelatine shell is composed only of gelatine and water and contains no plasticisers eg glycerol or sorbitol. This absence of plasticisers reduces the interaction between the shell and the fill and minimises the permeability of the fill through the shell. This means that hard gelatine capsules can be filled with fish oil, garlic macerat or valerian formulations, without the risk of odours.

Some products can only be prepared as a very thick paste with a high melting point. The high temperature threshold of Licaps, which may be filled at temperatures of up to 70°C, facilitates the filling of such products as hot melts; the process is then reduced to a straightforward mixing and filling operation.

conclusion

An ever more competitive market means that dietary supplement manufacturers need to choose the right encapsulation method to meet both the needs of production and the demands of their customers. Licaps is a unique and highly effective method of encapsulation that combines consumer appeal with innovative manufacturing technology.

Capsugel's distinct advantage lies in its unique LEMS technology and tightly controlled production process. These help to eliminate contamination or leakage problems, ensuring consistency, security and quality. Capsugel has recently enhanced its production with a dedicated centre in Colmar, France, for researching, developing and manufacturing its products.