To maximize your success in drug substance development, we offer the ability to not only screen and select a form of optimal properties, but also to develop an understanding of the processes that ensure consistent material for development, clinical trials and formulation.
Polymorphism is the existence of a drug substance as two or more crystalline phases that have different arrangements and/or conformations of molecules in the crystal lattices. The presence of multiple polymorphs of the active pharmaceutical ingredient (API) is particularly challenging with solid, oral dosage drug products. Our experts can help you develop a robust crystallization process that consistently produces the desired polymorphic form of the bulk API.
In some cases, the physical and chemical properties of two solid forms of a drug vary dramatically and have a significant impact on pharmacokinetics, ease of manufacturing and dosage form stability. Properties that can differ among solid forms of a substance include color, solubility, crystal shape, water sorption and desorption properties, particle size and shape, hardness, drying characteristics, flow and filterability, compressibility and density.
In a drug substance, these variations in properties can lead to differences in dissolution rate, oral absorption, bioavailability, toxicology results and clinical trial results — and can affect both the safety and efficacy of the different solid forms. Furthermore, stability presents a special concern, since it is easy to inadvertently generate the wrong form at any point in the development process. Because energy differences between forms are usually relatively small, form interconversion is common and can occur during routine API manufacturing operations, drug product formulation, storage and use.
Encountering a new solid form during late stages of development can delay filing, and the appearance of a new form in drug product can lead to product withdrawal. For this reason, pharmaceutical manufacturers often select a drug substance polymorphic form that has the characteristics that will aid in the manufacture of the drug product formulation.