Ensuring Stability the Biggest Amorphous Challenge for 88.2% of Developers

Pharma IQ

The use of amorphous pharmaceutical materials is widely considered an effective way of improving favourable drug properties and the latest findings from Pharma IQ suggest that many developers consider them an essential resource. But as Marc Descamps, Professor in Solid State Physics at Université Lille, recently noted, there are important considerations to make when formulating an amorphous substance.

He explained: "An amorphous state is an interesting formulation opportunity for poorly soluble drugs. That means when solubility is very limited in the crystalline state. So if you formulate in the amorphous solid state, which means glassy state, the solubility can be much higher.

"The factors which must be considered are those which have an impact on this stability. The main factor to consider is the molecular mobility because the structure does not change as the glass transitions. It is not really a structure problem but a mobility problem."

In a recent Pharma IQ survey, conducted ahead of the Amorphous Pharmaceutical Materials event scheduled to take place in Amsterdam, in September 2011, issues regarding stability were found to be among the biggest challenges faced by drug companies using amorphous forms.

The importance of amorphous materials

Pharma IQ's research revealed that the vast majority of drug companies consider using amorphous pharmaceutical materials at some point in the product development process. However, the stage at which amorphous forms are used appears to vary from firm to firm.

When asked to disclose how they view the role and importance of amorphous materials in enhancing drug properties, 35.3 per cent of respondents said that they only consider using them as part of an experimental approach. Just over 47 per cent of participants would use amorphous forms during initial concept and opening design stages.

Meanwhile, 35.3 per cent suggested that they were best reserved for formulation and drug development after a few initial failures. The suggestion that drug companies increasingly recognise the potential value of using amorphous compounds was highlighted by the fact that no respondents described them as a mere last resort when all else fails. Pharma IQ went on to poll delegates on the extent to which they see amorphous forms as being crucial to improving favourable drug properties. More than a third of participants agreed that amorphous pharmaceutical materials were a 'necessary' part of the process. While 47.1 per cent viewed them as a non-essential but 'recommended' consideration, less than a quarter believed the use of amorphous compounds to be 'optional'.

An emerging trend in amorphous forms

When he spoke to Pharma IQ, Marc Descamps, who is also Lead of the European ID Network for Improved Drug Efficacy and Availability – and an expert speaker at the Amorphous Pharmaceutical Materials 2011 event in September – discussed the outcomes of his collaboration with several large drug companies on past projects.

Asked whether he thought industry and academic partnerships were becoming more commonplace, he said: "My experience in this domain is very, very positive. We could have very fruitful collaboration with the companies, not simply from making measurements, but to capture even the fundamental aspects of the problem. And there are more and more fundamental researchers in companies with which we can discuss at a very high level.

"There is a very rapid evolution, I feel, in this domain. I believe that ways of thinking are evolving fast on both sides - industry and academic - which become closer together. Probably in this time of crisis developing such collaboration is a win/win process. That’s my perception."

Amorphous materials in practice

Respondents to the recent Pharma IQ survey also gave insight as to whether their organisation would have sufficient internal capabilities to construct amorphous forms on a large scale. Perhaps unsurprisingly, only 37.5 per cent of delegates saw in-house manufacture as a possibility in this area. Almost two-thirds, or 62.5 per cent, believed that their company or institution's own resources would be insufficient.

However, when participants were asked whether they currently use the outsourced services of CROs to design, construct and manufacture amorphous forms, 70.6 per cent said that they did not. In fact, only 17.6 per cent of respondents were from organisations outsourcing design, construction and manufacture of amorphous materials. Meanwhile, 5.9 per cent said that CROs were being brought in at the design stage only.

Pharma IQ went on to ask participants in its survey whether they saw the use of amorphous forms to enhance drug properties becoming standard industry practice. The vast majority, some 82.4 per cent, predicted that this would soon be the case, while just 5.9 per cent disagreed with certainty.

Key challenges

As well as discussing the latest industry advances and the best solutions for overcoming negative drug attributes during solid state development, the Amorphous Pharmaceutical Materials 2011 event will give the pharma community chance to learn from as-yet-unheard case studies tackling the key amorphous challenges. These include the need to ensure stability through the development pipeline and IP updates on the regulatory issues affecting application of amorphous compounds into solid state form.

The Pharma IQ survey polled respondents on what they themselves believed were the main challenges when constructing amorphous forms. Ensuring stability was the key concern acknowledged by 88.2 per cent of companies. The second-biggest challenge, cited by 35.3 per cent of delegates, was the scale up and manufacture of amorphous forms, while submitting a patent application had proved to be the major difficulty experienced by 11.8 per cent. For 23.5 per cent of participants, it was actually finding a suitable form that presented the major challenge.