A wide range of capabilities and a unique business model has drawn talent to a speciality pharmaceutical company.

Robert Becker, PhD, joined Eurand as chief research officer, a newly created position, in April 2009. He is responsible for overseeing all global research and formulation activities worldwide. Becker joined Eurand with nearly 25 years of pharmaceutical industry experience, including leading positions at Boehringer-Ingelheim, Eli Lilly and Biogen Idec. He holds a degree in Chemistry and a PhD in Physical Chemistry from the Technical University of Munich.

"I first became aware of Eurand’s drug delivery technology expertise in the late 1990s when I had to solve a few drug delivery challenges at Boehringer- Ingelheim," says Becker. "Since that time, I have interacted with Eurand scientists on multiple projects, and I was always excited about the company’s expertise, experience and creativity in overcoming complex and challenging drug delivery tasks."

This experience and creativity is supported by a range of proprietary technology platforms including bioavailability enhancement (Biorise), modified release delivery (Diffucaps), taste masking via microencapsulation (Microcaps) and orally disintegrating tablets (AdvaTab ODT). With the company’s broad project experience, extensive network of company relationships as a contract development organisation, and sound scientific knowledge, Eurand is a reliable partner for demanding development activities. Most recently, the company co-developed a new ODT formulation of Lamictal (lamotrigine) with pharmaceutical partner GlaxoSmithKline, which was approved by the US Food and Drug Administration (FDA) in May 2009.

New role ushers in a paradigm shift

Eurand’s R&D activities are subdivided into two key areas: 1. customer business with the focus on oral drug delivery, and 2. creation of a pipeline of innovative pharmaceutical specialities of its own. Research and development will become an even greater contributor to Eurand’s success and growth. The position of chief research officer was created to consolidate the company’s core technologies and expand on the existing technology platforms by identifying new formulation principles. ‘This will enable the company to augment its competitive position in the field of drug delivery partnering and strengthen its role as an integrated pharmaceutical company,’ adds Becker.

Larger pharmaceutical companies run a large and complex R&D engine, which requires well-defined structures and processes. On the other hand, sufficient room for creativity and innovation is also a necessity. Combining large pharma R&D management skills with the flexibility of a smaller company – and ensuring continuous flow of information along the R&D path – will capitalise on Eurand’s position in a growing competitive environment. ‘After having established the most effective infrastructure, Eurand’s R&D organisation will be able to leverage its innovation potential to advance the shift toward an integrated pharmaceutical company,’ says Becker.

The company has already begun to develop its own diverse product portfolio. Zenpep, for example, a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency, has recently been approved by the FDA. The product was developed leveraging the company’s proprietary drug delivery technology platforms. ‘Robert’s extensive experience in product development will help to fuel our continuing growth as a speciality pharmaceutical company focused on the gastroenterology market,’ says Gearoid Faherty, chairman and chief executive officer.

With such a mandate for growth and development, and a creative and innovative environment, Eurand is an exciting prospect for talented scientists. ‘Everybody in our R&D organisation is highly motivated to support the continued growth of the company and to search for new product development opportunities,’ Becker says. ‘There is a spirit and mindset here that everyone shares – to build Eurand’s future.’

Eurand is a global speciality pharmaceutical company that develops, manufactures and commercialises enhanced pharmaceutical and biopharmaceutical products based on its proprietary drug formulation technologies. Eurand has had six products approved by the FDA since 2001 and has a pipeline of products in development for itself and partners.

For more information, visit: www.eurand.com

Solving solubility

The insoluble nature of some compounds prevents the oral dosing of the treatments they enable. Innovation and precision engineering in equal measures have now overcome that problem, so that insolubility is no longer a barrier to oral delivery.

The preferred route of drug administration is oral dosing, either as a capsule or a tablet. Unfortunately, many compounds that may provide effective therapy either cannot be delivered in this way or are delivered sub-optimally in pill form. As more insoluble compounds exit discovery and drug safety, and as effectiveness becomes ever more crucial, technologies that enable compounds to be delivered in this way are increasingly in demand.

"Many compounds are highly efficacious or active at their therapeutic target, but they cannot be dosed orally," says Stephen Perrett, vice president, Portfolio Development for speciality pharmaceutical company Eurand. "Pharma needs a technology to change this and in Biorise we have just that. Biorise renders drug substances in an activated form, which is able to pass into the body when swallowed. Importantly, the chemical nature of the drug is not changed, meaning that its original efficacy and safety remains relevant. In addition, the final product is a dry powder that can be delivered as easily as a capsule or tablet."

Specialist expertise

Eurand develops, manufactures and commercialises enhanced pharmaceutical and biopharmaceutical products. Through its ability to combine a range of proprietary pharmaceutical formulation technologies with state-of-the-art US and European manufacturing facilities, it is a recognised leader in its field.

"We have one of the broadest oral drug delivery technology platforms in the sector," says Perrett. "It is a huge challenge to reliably and reproducibly apply a technology to such an extent that it becomes a commercial reality. This is evidenced by the multiple products sold globally that contain our technologies. Our most recent approval was Amrix, an extended release formulation of cyclo benzaprine, which is marketed in the US by Cephalon."

Biorise technology is commercialised in Europe by Novartis in the product Mesulid Fast, a fast-onset formulation of the NSAID pain-reliever nimesulide. As well as allowing drugs to act more rapidly, Biorise also allows Eurand to take a water-insoluble compound, one which would not be absorbed and would pass through the body when swallowed, and transform it so that it can be absorbed and hence provide effective therapy.

The Biorise process transforms drugs to a nanocrystalline or amorphous state, which is highly activated and would normally rapidly revert back to its original insoluble crystalline form. This is prevented by the use of stabilising materials, which are already used in marketed pharmaceutical products.

What the Biorise process does is just as important as what it does not do: it does not modify the chemical nature of the drug, it does not necessitate the introduction of any solvents or unapproved materials, and it does not expose the drug to heat stress.
"In the amorphous state, the drug molecules are in a condition similar to their being in solution," explains Perrett. "We can prevent these molecules from reverting to a crystalline state using our carrier systems, which expand only when they contact water in the body. This results in a liberation of the stabilised molecules that can then rapidly pass into the body through the digestive tract."

Improved bioavailability

Biorise has caught the industry’s imagination through its ability to produce amorphous drugs that are in a form akin to their being in solution, despite the fact that they are insoluble. "It’s a simple and contained process," says Perrett. "In one step you have a dry powder. We are creating new therapies because we can make new effective compounds dosable. Without this there can be no pharmaceutical product."

Biorise has important applications for existing drugs. It can increase the speed of drug absorption, which is particularly important in pain relief. It is not uncommon for a drug to have less than 50% oral bioavailability in marketed forms. By maximising their bioavailability, a reduced amount of drug can be used for equivalent therapeutic effect, meaning the product is safer and more likely to have a consistent therapeutic effect.

Eurand is building on the bioavailability enhancement platform technology, incorporating a focus on sustained release applications of poorly soluble drugs. This innovation has already opened up a route for the oral delivery of many compounds.

Eurand is a global speciality pharmaceutical company that develops, manufactures and commercialises enhanced pharmaceutical and biopharmaceuti¬cal products based on its proprietary drug formulation technologies.

Visit: www.eurand.com

New life for drug compounds

Drug solubility is an important factor influencing the rate and extent of drug absorption, therefore determining the overall bioavailability. Bioavailability technologies offer solutions that overcome the challenges of poor drug solubility.

Of all the new chemical compounds screened at the drug discovery stage, only a fraction make it through to market. Although companies employing modern drug discovery techniques, such as high throughput screening and combinatorial chemistry, are generating more drug candidates than ever before, most never make it past the first hurdle. The fact that about 60 to 80% of drugs coming directly from synthesis have solubility below 0.1mg/ml could be a factor contributing to this high attrition rate.

Application of bioavailability enhancement technologies could have a positive impact on these statistics and help the pharma industry improve its R&D productivity by allowing the development of products that may otherwise have been discarded. ‘On the clinical side, these technologies enable the development of oral dosage forms with improved bioavailability, faster onset of action, potential for improved tolerability and overall enhanced product performance, says Steve Ellul, director of business development for Eurand.

Enabling technology

Eurand’s Biorise technology creates drug nanocrystals and/or amorphous drug with enhanced solubilisation properties, faster absorption and increased absolute bioavailability. These ‘activated forms are then stabilised in an inert biological carrier, generally a polymer, to prevent the processed drug from reverting back to its crystalline form.

Eurand began working with Biorise in 2000, when it acquired the technology along with its originator Vectorpharma. Since then, Eurand has worked with pharmaceutical partners on confidential development programmes using Biorise.

"The technology increases the rate of dissolution of the drug allowing faster and more complete absorption, therefore lowering the administered dose and reducing the capsule or tablet size needed," says Ellul. "It’s aimed at drugs with poor water solubility in the gastrointestinal tract, making them easier for patients to take and increasing their therapeutic value compared with other potential competitors in the class."

One compound benefiting from bioavailability enhancement is Nimesulide, a non-steroidal anti-inflammatory drug approved and marketed in Italy by Novartis and Italfarmaco. Using Biorise, Eurand was able to achieve a formulation with more rapid onset-of-action without increasing overall drug exposure. "Biorise enables drugs that may otherwise not be developed," says Ellul. "However, it has utility in the development of improved formulations of currently marketed, poorly soluble drugs. It can be applied at any stage of drug development."

Unique challenges

One of the major challenges in creating amorphous and/or nanocrystalline materials is maintaining their stability.

"Keeping these materials stable for two years is key to the success of our approach," says Ellul. "Otherwise, such materials would naturally reaggregate into their original state and the benefit of the technology would be lost. Eurand has demonstrated the ability of Biorise to maintain stability in its activated state for long periods."

There are many ways to tackle poor bioavailability, and different companies address it in different ways. "There is no one-size-fits-all technology," adds Ellul. "For some drugs one technology will work; other drugs may require a different approach."

Another related challenge is the development of controlled release formulations of drugs exhibiting pH-dependent solubility profiles. Controlled release formulations require uniform and prolonged release of drug as the formulation passes through the GI tract. With drugs that are soluble in acid conditions, but are poorly soluble at the higher pH levels of the small intestine, this becomes very hard to achieve.

Eurand’s Diffucaps technology is a flexible multiparticulate system that has been adapted to enable once-daily formulation for drugs with pH-related solubility issues. Diffucaps creates and maintains an acid environment in the microparticle, allowing a drug to be released and absorbed along the entire GI tract, despite changes in pH.

‘The ability to achieve absorption and efficacy, and to create sustained and controlled release formulations is of great value to pharma, says Ellul. "By providing improved product performance, extended patent life and broadened therapeutic applications, bioavailability enhancement technologies breathe new life into drug compounds that might have fallen by the wayside."

Company profile

Eurand is a speciality pharmaceutical company that develops, manufactures and commmercialises enhanced pharmaceutical and biopharmaceutical products using its proprietary drug formulation technologies.

For more information, visit: www.eurand.com