CRYSFORMA: Polymorphism and crystallization, key issues in drug development according to international health security

Are you looking for a stable polymorph of your drug substance? Do you want to avoid any manufacturability, bioavailability or clinical outcome affection during your drug development or storage due to any unknown solid form conversion? Or even do you need to demonstrate to regulation authorities your valid results?

Chemical substance exists in the solid state in different crystalline forms. This property is called polymorphism.

European Medicines Agency (EMA)

Polymorphism is “the property of a chemical substance to exist in the solid state in different crystalline forms”, according to European Medicines Agency (EMA). This is one of the drug properties that affects pharmacological efficacy and toxicological safety and, as EMA states, it must be provided for health security. And these crystallization studies are carried out by Crysforma, the technology development unit from the Institute of Chemical Research of Catalonia (ICIQ-CERCA).

These different forms of an active substance may affect processability, stability, dissolution and bioavailability of the drug product. They can have different physical and chemical properties, and thus can have an influence on the bioavailability of the pharmaceutical compound.

The existence of different polymorphs is crucial in developing a patent strategy, as each distinct form may offer a basis for independent intellectual property claims. It is also important to understand the stability of the polymorphs to prevent undesired transformations during production of the active pharmaceutical ingredient or in the final pharmaceutical compound.

Polymorphism is a matter of crucial importance in the pharmaceutical industry. Accordingly, Crysforma offers comprehensive scientific assistance aimed at identifying and defining the most significant polymorphs, hydrates and amorphous phases of a drug, and to facilitate the selection of the most suitable candidate with optimal solid state properties.

How does it works

Crysforma has developed its own crystallization screening methodology based on the use of several crystallization procedures, oriented to obtain the thermodynamically stable phase as well as kinetically favoured phases.

A process that includes different type of studies:

• Initial or fast polymorphism screening for early stages candidates
• Comprehensive polymorphism study of a drug substance
• Determination of the relative stability of different polymorphs
• Scale-up of selected polymorphs
• Development of analytical methods for polymorph identification and quantification in drug substance and drug product
• Fast powder X-ray diffraction analysis characterization
• Crystallization of compounds that are difficult to crystallize or that are formerly known only as amorphous solids
• Crystallizations oriented to the generation of single crystals for single crystal X-ray diffraction structure determination
• Determination of the main physicochemical properties of the polymorphs (solubility, hygroscopicity, stability, particle size and morphology)