Absorption studies by remote control

Companies often extend the patent life of their top-selling products by developing modified-release formulations that reduce the number of pills taken and can sometimes improve safety and efficacy. However, selecting the best drug delivery system is far from straightforward.

Remote controlled capsules can be used to create a map of where compounds are absorbed in the tract. Then, with appropriate formulations, drugs can be designed that selectively deliver their payload in these areas, according to the report, which is published in Critical Reviews in Drug Carrier Systems.​

The benefits of extending the life cycle of a drug are clear. For example, GlaxoSmithKline lost patent protection last year for its antidepressant Paxil (paroxetine), which had sales of £2.1 billion (€3.2bn) in 2002.

This drug lost 40 per cent of its sales in the last quarter of 2003 as generic competition took hold, but as GSK has successfully migrated 30 per cent of users over to an in-patent sustained-release version - Paxil CR - the effects of the expiry have been mitigated.

"The adoption of Human Drug Absorption (HAD) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development,"​ said Ian Wilding and David Prior, two scientists working at UK company Pharmaceutical Profiles who authored the report.

Pharmaceutical Profiles is one of a handful of companies that have developed remote controlled capsule devices, which have existed in crude from since the 1960s.

Their product, called the Esperion, takes the form of a rounded capsule with a drug reservoir of around 1ml. It includes a spring-loaded piston that can discharge the contents of the capsule on demand using a radio frequency signal, and radiotracer to track its progress through the gut.

One of the main advantages of the device over its competitors is the active delivery system. Older capsules have tended to rely on passive diffusion of the drug, which can be a problem in areas of the GI tract, notably the colon, where there is not much free water to aid this process.

This active release system also broadens the range of formulations that can be tested using the device to include not only liquids but also particulates, viscous solutions, pellets and minitablets - all of which are used in the complex process of designing modified-release formulations. And the Esperion is smaller than its predecessors, making it more comfortable to patients to take and avoiding the gag reflex and the risk that it may get stuck in the stomach.

Esperion has already proved its value in guiding projects, according to Wilding and Prior. They cite a case in which a company was developing a pulsed delivery version of an existing drug based on data in animals, but terminated the project early after an Had study using Esperion showed that the approach would not work in humans. To date, around 1,000 of the capsules have been delivered to 400 patients in HDA studies.

And the technology is also finding applications in the drug discovery field. Product development scientists are increasingly faced with complex compounds coming out of technologies such as combinatorial chemistry.

Many of these compounds exhibit one or more undesirable properties, such as poor solubility in water, instability in GI fluids, poor permeability across the intestinal wall or a narrow absorption window in the upper small bowel. Using HDA and capsules such as the Esperion, scientists can select the best dosage form early on in the development timeline, raising the chances that a project will be successful.

As many as one in three drugs fail in Phase I clinical testing despite extensive pre-clinical screening of potential clinical candidates, mainly because of the lack of predictive power of drug candidate performance in man.

Earlier this month, Pharmaceutical Profiles​ reported that it had seen a 250 per cent increase in demand during the second half of 2003 for its HDA services.