Thermal Analysis of Reaction Mechanism

In recent years, evolving thermal analysis technique has been increasingly applied to the compatibility screening of drugs, because thermal analysis data can provide useful information on the chemical interaction between active pharmaceutical ingredients and excipients. At BOC Sciences, in order to provide fast and effective solutions, our scientists use different thermal analysis tools to identify interactions that affect the efficacy of active pharmaceutical ingredients. We are able to evaluate the reaction mechanism of drug-excipient interactions, which helps our customers design safe and stable dosage forms through the selection of optimal excipients. In general, we prepare binary mixtures by adding 0% w/w to 50% w/w API to excipient powders, and then perform thermal analysis using different types of thermal analysis instruments.

Figure 1. Drug–excipient compatibility screening using DSC. (Chadha, R.; Bhandari, S. 2014）

Advantages of Thermal Analysis

• Little sample consumption
• Reliable responses
• Forecast information for long-term conditions

Our Thermal Analysis Process

We have designed a systematic thermal analysis procedure to detect drug-excipient incompatibility and to explore the rate of reaction and reaction mechanism:

1) TGA analysis of API and excipients separately at 10°C/min

2) DSC analysis of API and excipients at multiple heating rates

3) DSC analysis of a 50/50 (wt.) mixture of API and excipients at 1°C/min

4) Measurement of reaction kinetics and reaction mechanism analysis: an Arrhenius plot is created using quasi-isothermal DSC at three temperatures, which can be used to obtain reaction kinetics and calculate conversion rate versus time. A series of techniques such as HPLC, IR, MS, XRD can be used for subsequent reaction mechanism studies

BOC Sciences’ Thermal Analysis Techniques

At BOC Sciences, we have introduced advanced differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to rapidly assess the drug-excipient chemical interactions:

Thermogravimetric Analysis (TGA)

Variations in the shape of the TG curve, mass loss, temperature of thermal events or the appearance of new thermal events indicate drug-excipient chemical interactions or incompatibilities. In the compatibility studies, we use TGA technique to observe the thermal degradation profile of the drug, the excipients and the mixture between them.

Differential Scanning Calorimetry (DSC)

DSC technique is widely used to evaluate the enthalpy variations over heating or cooling. At BOC Sciences, DSC measurements are performed for the API, the excipients and the mixture of the two components, respectively. The chemical interaction is determined by observing the appearance of new peaks in the mixture, the disappearance of peaks or the change in melting peaks (shape, position or enthalpy). If a melting peak is detected at the same temperature in the DSC curve of the mixture API+excipient as in the DSC curves for the individual components, this means that the API and the excipient are compatible. However, If there is a physicochemical interaction between the API and the excipient, instead of the two separate melting peaks, only one endothermal peak appears in the DSC curve of the mixture API+excipient.

Figure 2. Selected DSC scans of drug and drug-excipient physical mixture. (Monajjemzadeh, F.; et al. 2009）