Chemical Drug-excipient Interactions Studies

In general, the susceptibility of the reaction of an API with an excipient depends on the presence of possible chemical reaction pathways and the energy of the associated transition state. Small-molecule APIs have complex structures with different functional groups and can undergo multiple chemical reactions simultaneously or sequentially. In many drug products, even trace amounts of reaction products can easily lead to a final drug product that does not meet its expected key quality attributes. The main effect of API and excipient interactions is not only the loss of potency and intended therapeutic effect, but also the formation of potentially toxic or non-toxic degradation products. Therefore, it is critical for pharmaceutical manufacturers to understand the reaction mechanism and degradation products generated between drug and excipients. BOC Sciences provides comprehensive testing to investigate the reaction mechanism of excipient-drug interactions and properly characterize degradation products.

Chromatographic-based Identification of Degradation Products

Chemical interactions between APIs and excipients may lead to the degradation of APIs by generating unfavorable by-products or impurities. There are a variety mechanisms of API degradation including hydrolysis, dehydration, oxidation, isomerization, decarboxylation, dimerization, polymerization, photolysis and physical transformation. Degradation of APIs will result in drug products that do not meet the specifications for their potency and content uniformity. BOC Sciences’ state-of-the-art chromatography laboratory can strongly support our characterization services for the degradation products. Our chromatography experts are able to use HPLC and LC methods to separate impurities of drug-excipient interactions associated with the API degradation process, and combine MS, NMR and FTTR techniques for comprehensive identification of degradation products to help our customers fully investigate the chemical reactions between drugs and excipients.

Our Capabilities Include:

• Full understanding of the molecular scaffolding of excipients and APIs, and the structure of known reactivity sites
• Examine the possible mechanisms of chemical decomposition for the API in the context of the common functional groups that are present in the molecule
• Drug solution state stability studies (pH, thermal stability and photostability)
• Information of the formation of degradation products
• Degradation prediction models

Thermal Analysis for Reaction Mechanism

The importance of thermal analysis as a predictive tool for drug stability in the design of drug-excipient compatibility studies is undeniable. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) technique are rapid analytical methods that can satisfy most of preformulation studies. In general, thermal analysis techniques can be used to observe the thermal degradation of drugs, excipients and mixtures between them by providing imaging over time. At BOC Sciences, combined with microscopy and mass spectrometry that provide infrared and mass spectrometry analysis, we can elucidate and quantify the degration products. We prepare binary mixtures of API and excipients in a 1:1 ratio and then evaluate the purely separated samples and their physical mixtures using both DSC and TGA methods. Our expert teams can fully investigate the reaction mechanism by studying degradation kinetic data and conversion rate.

Figure 1. The role of DSC technique in the identification of chemical interactions between drug and excipients. (Gorain, B.; et al. 2018)

What We Offer:

• Reaction kinetic studies
• Conversion rate calculation
• Reliable thermal degradation profile