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
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