Glossary

API Characterization

API Characterization is the process of evaluating and defining the physicochemical and biological properties of an Active Pharmaceutical Ingredient (API). It typically involves identification of the molecular structure of the drug and its solid state – amorphous or crystalline, and determination of its particle size, solubility, stability, viscoelasticity, flow behavior and biological activity. As a fundamental step in pharmaceutical formulation, API characterization is performed with the application of various analytical methods such as UV spectrophotometry, high-performance liquid chromatography (HPLC), X-ray powder diffraction (XRPD), thermoanalytical techniques, and rheology.

In the field of thermal analysis, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) are widely used for the characterization of the molecular and macroscopic properties of pharmaceutical substances, and for investigation of the compatibility of the API and excipients, which may possibly be included in the final pharmaceutical product. You can see the application in table 1 below.

Rheology is the study of the flow and deformation properties of matter, and it is essential to understand and determine the viscosity, flow behavior, viscoelastic properties, and stability of pharmaceutical substances, see table 1.

Thermal and rheological characterization of APIs provide the basic information to support the pharmaceutical development described in different pharmacopoeias. In the US Pharmacopeia (USP), for example, general chapter 891 describes thermal analysis and chapters 911, 912, 913, and 1911 are dedicated to viscosity determination and rheological tests. International standards organizations like the American Society for Testing and Materials (ASTM) and the International Organization for Standardization (ISO) also describe standard test methods of such techniques.

Table 1: Thermal analysis applied in API characterization

	Property	DSC	TGA	Rheology
Molecular properties*	ideal solubility	x
	hygroscopicity		x
	Thermal StabilityA material is thermally stable if it does not decompose under the influence of temperature. One way to determine the thermal stability of a substance is to use a TGA (thermogravimetric analyzer). thermal stability		x
	oxidative stability		x
	Reakcja rozkładu (dekompozycji)A decomposition reaction is a thermally induced reaction of a chemical compound forming solid and/or gaseous products. decomposition onset	x	x
Macroscopic properties*	Melting Temperatures and EnthalpiesThe enthalpy of fusion of a substance, also known as latent heat, is a measure of the energy input, typically heat, which is necessary to convert a substance from solid to liquid state. The melting point of a substance is the temperature at which it changes state from solid (crystalline) to liquid (isotropic melt).melting point	x		x
	enthalpy of fusion	x
	Glass Transition TemperatureThe glass transition is one of the most important properties of amorphous and semi-crystalline materials, e.g., inorganic glasses, amorphous metals, polymers, pharmaceuticals and food ingredients, etc., and describes the temperature region where the mechanical properties of the materials change from hard and brittle to more soft, deformable or rubbery.glass transition temperature	x		x
	PolymorphismPolymorphism is the ability of a solid material to form different crystalline structures (synonyms: forms, modifications).polymorphism screening	x
	salt a screening	x
	eutectic purity	x
	viscosity			x
	viscoelastic properties			x
	formulation stability			x
	yield point			x
Substances interactions	release of volatiles	x	x
	plasticizing effect	x
	compatibility	x	x
	(thermal) kinetics	x	x	x

*Molecular properties are intrinsic and determined by the molecular structure, while the macroscopic properties are those derived from the intermolecular interactions.