Solid Form Screening and Selection

Solid form screening and selection is critical for the successful development of active ingredients. New chemical entities are facing increasing challenges in their physical properties (solubility, dissolution rate, ability to crystallize, stability, etc), and the selection of the right crystalline form is a fantastic way to optimize their physical attributes. Plus, it offers and excellent entry to novel intellectual property.

Salt or cocrystal selection, where physicochemical properties of the molecules can be modulated to suit your development strategy. The formation of a salt or cocrystal will depend on the ability of the drug candidate to ionize (pKa) or in the ability to exploit other interactions (H-bonds or stack interactions) respectively. Other factors depending on the specific application will be taken into consideration to design a screen with high chances of success.

In the pharmaceutical industry, regulatory authorities require that companies have full control on the physical properties of their development candidates, to ensure that no changes will occur during later development, manufacturing or even commercialization that may affect the performance or safety of the drugs. Performing a polymorph screen early during development will help you greatly to manage the risks associated to solid-solid transitions or new potential polymorphs appearing later that may alter the behavior of the drug causing potentially large costs of re-working existing batches and potential losses of revenue if the drug has to be withdrawn from the market. A phase appropriate polymorph screen design will help you manage the risk without committing more resources that are necessary depending on the development stage of the drug.

Other less regulated industries can also benefit from the selection of an optimal solid form depending on the intended application. A deep understanding of the physical properties of the molecules will be useful to understand the potential challenges that that form may encounter during development or manufacturing and will feed back into the design of the active ingredients to optimize the physicochemical attributes that will make them more likely to succeed depending on their specific application.

Understanding the crystallinity behavior of the molecule, as well as its thermal properties, hygroscopicity, etc. will help us evaluate the fitness of the current form for development and will establish the basis against which different batches of material produced should be measured.