Development of your API: Why is solid state science important?

For a newly discovered solid chemical entity as an API, one of the characteristics to establish is the aqueous solubility. Another property which is also used to define a drug substance is the melting point. For a substance to melt, energy is required; this process is described as endothermic. This is a thermodynamic property of the solid and is termed the enthalpy.

Variations in the melting point and enthalpy can be indications of the presence of impurities, not only chemical, but crystallographic. The latter might be an indication of polymorphic behaviour of the compound - which is how the molecules of the compound pack together in different arrangements in the crystal lattice - and will modify the physicochemical properties which might be detrimental to the solubility of your API.

As the investigations into the drug substance are progressed, there are a number of properties that need to be considered, primarily hygroscopicity, the behaviour of the solid to variable humidity. This can have implications for the API and drug product manufacture.

Solid defining characteristics such as particle size and shape can influence the colour, density, flowability and millability for particle size reduction and chargeability. Other mechanical properties which might have an influence upon the dissolution behaviour in the drug product are hardness and compactability of the API.

Whilst some of the latetr solid attributes will come to light as material becomes available and as drug product formulation development is undertaken, variations in melting point and enthalpy should not be overlooked and an assessment of the propensity of the new chemical entity or salt thereof to polymorphism should be evaluated. Regardless of where your API is, investigational early phase or on the development road, MorphCryst Consulting can offer advice and ensure that progress is maintained.