Drug-excipient Compatibility Studies

The main role of excipients is to aid in the production, release or absorption of active pharmaceutical ingredients. In addition, excipients also play a role in improving odor or maintaining product performance. However, excipients may sometimes chemically or physically interact with the API. Determining the existence of these interactions and accurately measuring them are critical steps to obtain stable solid dosage form. Once it is proven that an interaction between the API and the excipient does exist, the necessary steps can be taken to prevent such a reaction. However, visual or visible incompatibilities are difficult to detect. Thanks to the development of thermal and spectroscopic techniques, researchers can gain insight into physical or chemical drug-excipient interactions. BOC Sciences provides comprehensive services for compatibility studies of commonly used pharmaceutical excipients and active ingredients. Our laboratories are equipped with advanced thermal analysis and spectroscopic analysis instruments to help our customers predict, monitor and characterize the incompatibility in pre-formulation studies. For ingredients belonging to different therapeutic areas, our experts use different methods and techniques to study these complex drug-excipient interactions.

Figure 1. Evaluation of compatibility between acarbose and common excipients. (Gholizadeh-Hashjin, A.; et al. 2021)

Classification of Drug-excipients Interaction

• Physical interactions include glass transformation, fusion, vaporization, sublimation, desorption and absorption, which can promote changes in appearance, drug release profiles, polymorphic forms, taste, odor or solubility. Physical interactions can affect dose uniformity, the rate at which an active ingredient dissolves in the gastrointestinal tract, or make administration more difficult.
• Chemical reactions include desolvation, dehydration and redox reactions; chemical incompatibilities are associated with drug degradation, resulting in loss of drug potency and possible formation of other unwanted molecules. Chemical interactions can lead to degradation of the active ingredient in the drug, reducing the amount of active ingredient available for treatment.

Our Capabilities

At BOC Sciences, we perform binary mixture compatibility testing to rapidly screen the potential incompatibilities. And our team utilizes spectroscopic and microscopic techniques as well as thermal methods to assess the a variety of drug-excipients interactions.

Binary Mixture Compatibility Testing

Binary mixture compatibility testing is another commonly used method for testing the compatibility. In this method, a binary (1:1) mixture of drug and excipient is tested for compatibility by compaction or preparation into a slurry. The mixture is then analyzed by high performance liquid chromatography. At BOC Sciences, we provide differential scanning calorimetry analysis service to complete a rapid screening of potential incompatibility.

Chemical Drug-excipient Interactions Studies

Even trace amounts of reactive impurities in a drug can lead to serious drug stability problems, since the amount of excipients in a formulation often far exceeds the weight and quantity of the API. Our expert teams identify the formation of reaction products to analyze potential chemical interactions.

• We employ thermal analysis techniques to determine the chemical reactions and explore the reaction mechanism through the obtained kinetic data and conversion rates
• At BOC Sciences, a series of advanced chromatographic techniques are applied to separate and characterize the degradation products generated between drug and excipients

Physical Drug-excipient Interactions Studies

The investigation of physical interactions helps to optimize the physical properties of excipients by adjusting key process parameters.

• In order to prevent the drug aggregation, BOC Sciences has introduced a variety of thermal analysis techniques, microscopy and spectroscopy instruments to identify and evaluate the adsorption behavior
• The complexing agents in the formulation may interact with the drug to form complexations. Our experts offer API-excipient complexation testing services to help ensure good compatibility between your drug substance and the excipient material
• For the formulation optimization of amorphous drugs, we determine whether drug-excipient interactions are formed in the solid dispersion and thus determine the stability