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.

Kriechen (Rheologie)Creep is one of the earliest “controlled stress” rheometer tests that quite literally “creeps” the material, i.e. we measure over a relatively prolonged period the small movement (the creep defined as creep compliance, J) of the sample by applying a small constant stress.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

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