Seeing through formulation problems
providers of analytical services for the solid state
characterisation of their formulations, seeking answers to
processing issues, drug delivery challenges and even protecting
drug patents.
The introduction of the Process Analysis Technologies (PAT) initiative by the US Food and Drug Administration (FDA) as well as the search for new drug delivery platforms have resulted in a surge of interest in physical and chemical characterisation, with analytical firms such as Molecular Profiles and CSMA cashing in on the action.
This is because there is a correlation between a drug's structure and its function, stability and release profile.
With the average cost of developing a drug at $1bn (€0.78bn), in a process that takes around 15 years, pharma companies are pushing for a fundamental understanding of a compound's physical and chemical properties as early in the pipeline as possible.
These properties include the drug's particle size, shape, roughness, cohesion, flow properties and dissolution. They also extend to the drug delivery system used, its composition, distribution, compatibility, segregation and degradation.
Any solid dosage form, be it tablets, capsules, granules, implants or stents, can be analysed.
"The analytical instruments that pharma companies use are geared towards bulk so they when they don't have enough imaging power to see what they want they come to us," Alan Brown, CSMA's director of technology, told In-PharmaTechnologist.com.
"We have expertise and instruments with a high level of optical design costing as much as $1m which big pharma does not have."
Drugmakers seek the services of specialists like CSMA when they wish to optimise a drug's delivery or when a formulation causes production problems that they cannot resolve.
Surface technologies allow precise comparisons between batches and can reveal contamination, processing issues and poor tablet integrity.
They are even useful with non-solid dosage forms when evaluating product and packaging compatibility; in developing Exubera, its inhalable insulin device, Nektar asked Molecular Profiles to use atomic force microscopy (AFM) in order to assess the viscoelastic response and surface-free energy of the product.
"Different techniques will give different kinds of information and selecting the right tool for the job is important," Claire Madden-Smith, commercial director of Molecular Pofiles, said in a speech at the Controlled Release Society's annual meeting in Vienna.
"How to prepare and handle samples is also important, you can have non-intrusive virtual sectioning so you can reuse the sample or you can have physical sectioning with a microtome."
Apart from AFM, scanning electron microscopy (SEM) and confocal laser scanning Microscopy (CLSM) are popular in physical analysis, while X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) are two of the most important chemical surface analysis techniques.
Some of the analytical firms big pharma employs, such as CSMA, use their imaging technologies also in other areas, ranging from aerospace to ceramics, while others, such as Molecular Profiles, work solely with the drug industry.
The fact that these companies are independent becomes particularly important when their services are used for patent and litigation support; reverse engineering and deformulation can often determine if two products have been made the same way, providing a useful weapon to pharmaceutical companies that fight to protect their branded drugs from generics.
This kind of work is also useful in detecting counterfeits, which according to the World Health Organisation currently account for ten per cent of the global pharmaceuticals market.
As drugmakers strive to understand the complex interactions that take place between the surfaces of the product, plant equipment and packaging throughout the manufacturing process, the market for such analytical services is bound to keep growing.
