A not-so-bitter pill to swallow

Taking a pill does not have to be an unpleasant experience. GeneviEve Garrigos, Dpharm, of French drug delivery company Ethypharm, discusses the benefits of tablets that are pleasant tasting and disperse quickly in the mouth

Usually, when you pop a couple of tablets in your mouth without liquid two things happen: first, you are unable to swallow the pills; and second – and probably worse – they taste horrible. This is even more of a problem for young children or the elderly who find it physically difficult to swallow.

Pleasant-tasting and rapidly dispersible tablets are being demanded increasingly by patients, consumers and physicians, requirements that scientists at French drug delivery specialist company Ethypharm aim to meet with their new Flashtab technology.

This proprietary process results in a multiparticulate tablet that:

To date, versions of otc analgesics have been the main focus of developments, and paracetamol is marketed in Europe, the US and South America. But several projects are currently under development, including antimigraine, antihistaminic and psychotropic indications.

The medicines are produced using a two-stage process. The initial step involves the manufacture of the drug as a dry powder or granules. This is done by coating crystals of the active ingredient using acrylic polymers that exert no apparent influence over its pharmacokinetic profile, while acting to mask its natural taste. The coated particles are compressed into pellets by dry-blending to a compression ballast, which allows the pellet to disintegrate rapidly in contact with saliva.

A key feature of the technology is that the particles behave differently under the different pH conditions of the gastrointestinal (GI) tract, At pH7.5 – the pH of saliva – the tablet breaks down in less than 30 seconds of contact into a taste-masked and flavoured suspension, ready to swallow. However, the coating of the active ingredient does not dissolve yet.

Between the oesophagus and the stomach, the conditions in the GI tract become increasingly acidic, and can attain values below pH2.0. In this environment, the polymer coating dissolves completely in less than 10 minutes, allowing the absorption of the drug through the mucosal membrane.

onset of action

The taste-masking feature is predicted to improve treatment acceptability by the patient, especially by children, thus contributing to better compliance and improvements in the clinical performance of the treatment.

Furthermore, the bioavailability of the active ingredient is equivalent to the classic formulation of the same drug, but the multiparticulate structure of the products means that the inter- and intra-subject variability is limited compared with 'monolithic' forms. Flashtab drugs also exhibit faster onset of action and reduced local toxicity on the digestive mucosa compared with monolithic forms of the same drug. This is because absorption of the active ingredient is spread over a much larger area when it disperses into the upper GI tract.

By contrast, existing tablet formulations can induce a high local concentration of the active ingredients in contact with the digestive mucosa, which can be toxic and painful, and can lead to mucosal perforation in extreme cases.

Ethypharm's technology should allow for much higher dosage forms of active ingredients – up to 650mg – without presenting such toxicity issues.

market requirements

Finally, the technology can also make use of a broad range of flavours, which enables it to be adapted to specific market conditions and requirements.

As consumers and patients are increasingly demanding more convenient medicines with improved characteristics, so companies are trying to find innovative ways to exploit large pharmaceutical markets. Ethypharm believes its new formulation will address these needs.