Binary Mixture Compatibility Testing

Compatibility studies can rapidly identify important changes in the drug formulation, such as changes in melting point or glass transition. Binary system of drug and excipients are typically employed in the preformulation studies. Binary mixtures are evaluated in a 1:1 ratio of of pure isolated samples and their physical mixtures, which allows for enhanced interactions in order to obtain better visualization of possible instabilities over time. Thermal analysis techniques are widely used in the interaction studies between active ingredients and excipients, degradation kinetics and stability studies of drug dosage forms. A range of thermal analysis techniques can be combined with microscopes providing time-dependent imaging, infrared and mass spectrometry analysis to elucidate and quantify the products generated by excipients and APIs. At BOC Sciences, we prepare and synthesize the binary mixture to find and optimize a general method of detecting the drug-excipient interactions, with the aim of predicting rapidly and inexpensively the long term stability of a pharmaceutical product and speed up its marketing.

Preparation of Binary Mixtures

In a typical drug/excipient compatibility testing procedure, binary powder mixtures are prepared by triturating API with the individual excipients. These powder samples, usually with or without added water, are stored under accelerated conditions. and then analyzing it by a Stability-indicating method, such as HPLC is used to analyze the binary mixtures. Alternatively, a binary sample can be screened using a thermal method, such as DSC/ITC.

Figure 1. Binary Mixtures of Some Active Pharmaceutical Ingredients with Fatty Alcohols. (Songhee, J.; et al. 2020)

Our Standard Testing Workflow

BOC Sciences provides a high-throughput drug-excipient compatibility test using the binary mixtures of drug and excipient. The experiment is planned and evaluated using a statistical experimental design combined with a series of thermal analysis techniques.

• Binary mixtures of drug and excipients commonly used in solid formulations are prepared in microtiter plates. After the synthesis process is completed, the samples are then exposed to different temperatures and humidity for different durations
• The binary mixtures are analyzed to identify possible chemical drug degradation
• Categorical statistical design is applied to identify the effects and interactions of excipient on drug degradation

Our well-designed process enables rapid identification of interactions in binary mixture, which helps our customers to quickly and rationally pre-select drug additives early in solid formulation development.

Analytical Methods

BOC Sciences has introduced the following techniques to be applied in the drug-excipient compatibility evaluation:

• Differential Examining Calorimetry (DSC): Provides the main physicochemical properties of the pure sample, such as melting point
• High Performance Liquid Chromatography (HPLC): Creates a reliable final decision in drug-excipient compatibility evaluations
• Fourier transform infrared spectroscopy (FTIR): Provides the variation of absorption spectra of the drug-excipient binary mixtures

Binary Mixtures Analysis

In the identification of physical or chemical incompatibilities, thermal analysis techniques are useful tools for the analysis of the binary mixtures.

• Firstly, our expert applies DSC as a screening approach to assess the compatibility of drugs with some of the excipients commonly used today
• Then, the binary mixtures of the drug and excipients are evaluated by HPLC technique, an we compare the chromatograms of mixtures to pure components to assess compatibility
• Lastly, we use IR spectroscopy to further investigate the binary mixtures, to prove whether any chemical interaction occurred