Drug-Excipient Compatibility Assessment in Pharmaceutical Formulations

Ensuring compatibility between an active pharmaceutical ingredient (API) and its excipients is a critical facet of drug development, influencing stability, efficacy and safety of the final dosage form. Incompatibilities may lead to physical changes such as polymorphic transitions or chemical reactions that degrade the API or generate impurities. Preformulation screening employs a combination of thermal, spectroscopic and diffraction methods to detect early signs of interaction. Thermal techniques—principally differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—provide rapid insight into melting behaviour, decomposition patterns and moisture loss. Spectroscopic methods, including Fourier transform infrared spectroscopy (FTIR), complement thermal data by revealing shifts in functional group vibrations indicative of chemical bond formation or cleavage. Powder X-ray diffraction (PXRD) uncovers changes in crystallinity or the emergence of novel solid phases. Advanced data-processing approaches, such as chemometrics and principal component analysis (PCA), enhance interpretation by distinguishing subtle variations in complex datasets. By integrating these complementary tools, formulators can optimise excipient selection, mitigate degradation pathways and ensure reproducible performance under accelerated and long-term storage conditions, thereby safeguarding both product quality and patient health.

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Drug-Excipient Compatibility Assessment in Pharmaceutical Formulations publication trend

The graph below shows the total number of articles in drug-excipient compatibility assessment in pharmaceutical formulations across all publications each year (not limited to Nature Index journals).

Technical terms

Active pharmaceutical ingredient (API): The biologically active component in a formulation responsible for therapeutic effect.

Excipient: An inactive substance formulated alongside the API to facilitate processing, stability or delivery.

Differential scanning calorimetry (DSC): A thermal technique measuring heat flow associated with transitions such as melting or crystallisation.

Thermogravimetric analysis (TGA): A method that records mass changes on heating, revealing degradation and moisture loss.

Fourier transform infrared spectroscopy (FTIR): A spectroscopic approach that identifies chemical bonds through characteristic vibrational frequencies.

Powder X-ray diffraction (PXRD): A technique for elucidating crystalline structures and detecting polymorphic forms.

Chemometrics: The application of mathematical and statistical methods to interpret complex chemical data.

Principal component analysis (PCA): A multivariate tool that reduces data dimensionality to highlight patterns of compatibility or interaction.

Polymorphism: The existence of a substance in more than one crystalline form, which can affect solubility and stability.

References

1. Application of TGA/c-DTA for Distinguishing between Two Forms of Naproxen in Pharmaceutical Preparations. Pharmaceutics (2023).
2. Thermal Compatibility of New ACEI Derivatives with Popular Excipients Used to Produce Solid Pharmaceutical Formulations. Pharmaceuticals (2024).
3. DSC, TGA-FTIR and FTIR Assisted by Chemometric Factor Analysis and PXRD in Assessing the Incompatibility of the Antiviral Drug Arbidol Hydrochloride with Pharmaceutical Excipients. Molecules (2024).