Amorphous Material Studies: Collaboration, Commitment and Compliance




Marc Descamps, Professor in Solid State Physics at Université Lille and Lead of the European ID Network for Improved Drug Efficacy and Availability, joins Pharma IQ to discuss the use of amorphous pharmaceutical materials to improve necessary drug properties.

Pharma IQ: Firstly, using amorphous pharmaceutical materials is considered to be an effective way of improving necessary drug properties. What are the important factors to consider when formulated an amorphous substance and why?

M Descamps:
Mainly, 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 problem, the drawback, is that glasses are intrinsically not stable state. They are prone to age, to re-crystallise, and that cannot be avoided. So the nature of the glassy pharmaceuticals depends on the sample history of the right of quenching, of drying, of shearing, as is the case when you prepare amorphous compounds by spray drying, by extrusion, etc. So the hue is to manipulate the glassy state to make it as stable as possible physically but also chemically while keeping solubility as high as possible. It is necessary, most often, to formulate HPI with excipients to increase the TG, for example.

The problem of solubility of HPI in polymer is a fundamental question.

So 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.

Glasses are classified according to the mobility properties. Mobility both above and below the glass transitions, and the position of the glass transition temperature is a direct signature of the mobility. Consequently the thermodynamics are very important also to consider because very recent fundamental research has shown that there are possible connections between thermodynamic and stability and the evolution of the mobility. It is thus necessary to use several complementary techniques to probe relaxation, to probe spectroscopy, calorimetry, and also structure, of course, to check the degree of homogeneity, for example, or to catch nucleation. It is also very important to capture the value of TG. It is what I can say at the moment on this problem of important factors to consider.

Pharma IQ:Thanks very much, Marc. That was a great summary. You have collaborated on projects with several large pharmaceutical companies in the past. Do you consider that industry in academic collaborations are becoming more commonplace, and does this represent a new trend in pharmaceutical R&D?

Marc Descamps: My experience in this domain is very, very positive. We could have very fruitful collaboration with the pharmaceutical 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.

Pharma IQ:Your research interests focus on phased transitions in molecular materials, disordered crystals, molecular glasses, and using physiochemical techniques to study the structural and dynamic properties of pharmaceutical solids. What impact is your research having or going to have on developments in new therapeutics?

Marc Descamps:For example, I can cite a few. Our research allows us to identify the factors which control the propensity to amorphise upon milling and dehydration, for example, and also to predict the value of the glass transition temperature, which is an important factor to predict the stability of the amorphous compound. Also, in terms of prediction of the phase diagram of polymeric excipient mixtures to localise the favourable zones in concentration and temperature. This leads to associate experiments and modelisation. We could provide some recipes in this domain. Another example is the mechanism of bio-protections of labial molecule by sugars. It allows us to better choose a bio-product in the way to use it. Other questions, for example, are related to the prediction of nucleation and growth conditions for the crystallisation problem. These are some aspects we have studied and on which we can have impact, which we studied recently.

Pharma IQ: At the conference in September, you will be delivering a presentation exploring the aspects of molecular materials transformed by milling and drying operations to induce phase and glass transitions of pharmaceuticals. What do you expect will be the key takeaway points from your talk?

Marc Descamps:What I hope is that some participants will have a better view of the different types of impact that these operations - milling, drying, etc - can have on the physical nature of the end product, and also on the chemical nature. They will have maybe a better view of how to fix the parameters of the process they use during formulation. For example, to modify the temperature of the grindings, intensity of grinding, in case of milling; and also to control the rate of dehydration, for example, the process of dehydration, which is so frequent in formulation. I hope this could help them to realise how the conditions of formulations may have an impact on the nature of the glassy state and the stability, both physically and chemically. If this is possible, it would be a good result for me.

Pharma IQ: We look forward to your presentation. Finally, Marc, to round off, at the event in September, what do you think will be the most valuable discussion points looking at the agenda, and what do you hope to gain from being there?

Marc Descamps: From my point of view, a lot is to be learned by, say, fundamentalists because people in the industry are very imaginative and it's very important for me, for example, to know the new formulation processes that people in industry can imagine. Another thing that could be important for me is to discuss the feasibility at the industrial level of the solutions that I could propose that academics could imagine. This leads to the important problem to capture the question of the incidents of scale up. I think that is very, very important. What is the impact of scale up and modifications in the formulation. For example, another question, which seems to me very important, is to discuss the question of disordered pharmaceutical materials, considering and indentifying the different levels of disorder. I think it is the biggest issue at the moment, I believe. So it is important to see the impact of these different levels of disorders. I mean intrinsic disorder, for example, when you have a glassy compound, the TG, etc, but also disorder at the more mesoscopic level, as influence of microstructure on the delivery, for example. It is my view and I am quite certain that I will learn a lot on this aspect.

IQPC

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