Crystal Form Selection

Crystal Form Selection close up

The properties of a solid influence its efficacy as a drug or excipient are highly dependent on form: Is it crystalline, amorphous, a hydrate? Selecting the optimum solid form for manufacture is critical to secure FDA approval of an NDA.
Almac has deep experience in the manufacture of APIs from microgram to multi-kilogram scale and beyond.

Our expertise ranges from synthesis to salt formation, and to specialised techniques for manufacture of cocrystals and metastable polymorphic forms. We can generate and characterise crystalline polymorphs, hydrates, solvates, de-solvated solvates, salts, and amorphous forms.

Our customers need to determine the optimal form of a drug as early as practicable in the drug development cycle (see table below). We work with you to plan a research protocol aimed at the selection of the best form of your compound for development and manufacture using a progressive approach. Almac Sciences follows a tiered approach to select the optimal physical form for your application: salt selection; polymorph and cocrystal screening; and comparative property determinations.

Properties of the API will vary depending on the solid form selected:

Bioavailability
Hygroscopicity
Dissolution rate
Solubility
Physical & chemical stability
Compressibility
Filterability
Flow

Melting point
Colour
Excipient compatibility
Crystal habit
Density
Taste
Toxicology

Form selection choices include:

Salts
Cocrystals
Crystalline forms

Polymorphs - same chemical composition, different solid state arrangement of molecules
Hydrates & solvates

Non-crystalline