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Pharmaceutical Manufacturing and Packing Sourcer

A Sweeter Deal

Orally dispersible tablets (ODTs) are growing in popularity and their market value could exceed $13 billion in sales by 2015, based on current global growth trends (1). Market studies have indicated that more than half of the patient population prefers ODTs to other dosage forms (2). Most consumers would also ask their doctors for ODTs (70 per cent), purchase ODTs (70 per cent) or prefer ODTs to regular tablets or liquids (over 80 per cent) (3).

The growth in the popularity of ODTs reflects the growth in the elderly and infirm population, who often find it difficult or unpleasant to take conventional tablets. ODTs fall apart in the mouth in contact with saliva, making it easy for a person to swallow the tablet without the need of water. ODTs, along with chewable and effervescent tablets, are also a convenient way to deliver active pharmaceutical ingredients (APIs) to children or those with dysphagia, nausea, vomiting and motion sickness, for example.

Over the past few years, there have been several innovations that have improved the appeal of ODTs. Key developments have been improvements in the speed of disaggregation of ODTs, as well as the growing use of non-hygroscopic, zerocalorie sweeteners, with off-taste-masking properties, which have helped make ODTs more palatable.

Creating ODTs

The challenges of developing ODTs are similar to those for conventional solid oral dosage forms. For instance, one of the main issues for both forms is the need to establish the active drug substance's compatibility with both the excipients and the process. For ODTs specifically, the key challenges are to produce tablets with rapid disintegration time and overcome the off-taste exhibited by many actives.

To overcome the off-taste, sweeteners and flavours are often included to achieve a palatable formulation. Additionally, a pleasant mouthfeel is also important. Developers are now addressing this by using an optimal selection of a sweetener/ binder system which has these characteristics, such as erythritol and isomalt.

These challenges can be overcome by using a wet granulation of erythritol. This excipient has the right requirements: it is non-hygroscopic, contributes to good mouthfeel and has off-tastemasking properties. In addition, robust tablets can be made via wet granulation and combined with a disintegrant to provide a faster breakdown. Erythritol also has taste-masking properties, as well as being zero-calorie, non-cariogenic (toothfriendly) and non-hygroscopic with a high-level of digestive tolerance, similar to sugars like fructose and lactose. This combination of properties makes it a very effective ingredient for tablets that need to stay in the mouth for some seconds while dissolving.

Studies into Erythritol as an Excipient

A recent internal study using L-ascorbic acid (vitamin C) as the active, erythritol as the excipient, and isomalt as the binder, was striking.

There are three specific areas where erythritol outperforms mannitol, the current most widely used polyol excipient in ODTs: dilution potential; disintegration profile; and tastemasking. For example, erythritol’s dilution potential was shown by the study to be much higher when compared to mannitol under the same production conditions. With an addition of 10 to 50 per cent of active ingredient, no significant loss of tablet quality is seen. For ODTs made using mannitol, on the other hand, a decrease of more than 75 per cent in hardness is seen for a formulation containing 50 per cent of active ingredient.

With regard to the disintegration profile, in tablets containing 10 per cent vitamin C and comparing erythritol to mannitol, variations in performance have been noted. The disintegration profile (even without the addition of a super disintegrant) was found to be much better for erythritol tablets than for the same formulations with the alternative excipient (see Figure 1). As disintegration times are one of the key factors in ODTs, this is a real benefit.

In terms of taste-masking, erythritol has well-documented properties relating to unpalatable compounds in food. This pilot study confirmed that the established taste-masking properties of erythritol as a food ingredient are just as effective with unpalatable pharma actives. Tablets made with erythritol were much more positively received by an internal taste panel compared to those with mannitol.

Mannitol continues to have a vital role to play with ODTs. However, where taste-masking and a high dilution profile are important, erythritol has genuine and distinct advantages.

A further study using acetaminophen (paracetamol) as the active and erythritol as the excipient, with mannitol as the comparison, was conducted in 2012; both were combined with isomalt as the binder. Early taste panel results have proved very encouraging, with erythritol once again exhibiting performance benefits in palatability and taste, and more extensive trials are planned.

Three particular problems have been solved by the use of erythritol as an excipient. It has become easier to create tablets of sufficient hardness for a given quantity of APIs, which in practice means tablets can made be smaller and thus easier for the body to process.

A superior disintegration profile has also been achieved without the need for a superdisintegrant, and the masking of unpalatable tastes associated with pharma actives has been achieved thanks to the off-taste-masking properties of erythritol, which means less need for flavourings.

A patent application for the use of erythritol in ODTs has recently been granted (4). This complements two other granted pharmaceutical patent applications, covering granulation of erythritol with sorbitol and isomalt as a binder to create acceptable-tasting chewable tablets with moisture-insensitive and moisture-sensitive actives respectively.

Although ODTs are potentially less robust than conventional solid-oral dosage forms, given their formulation to achieve rapid disintegration this can be easily overcome by paying careful attention to packaging requirements, for example using aluminium blister packs.

Looking Forward

Future innovation and developments in ODTs will probably be around marketing and awareness, as much as in particular technological solutions. Raising awareness of ODTs among healthcare professionals and developing market segmentation for specific end users is very important. In particular, ODTs will be useful as a way to manage costs with health budgets coming under greater pressure, as well as offering benefits in light of increasing life spans and a growing elderly population.

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Liesbeth Meeus is based in Cargill’s European research and development centre in Vilvoorde, near Brussels. She has a degree in chemistry and has held a variety of posts in Cargill, the latest being Application Technology Manager (Pharma and Personal Care, Confectionery, Beverages). Liesbeth’s focus has always been on applications in food, but beyond this she has growing experience in strategic involvement, people management, customer intimacy projects and intellectual property management.
Liesbeth Meeus
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