Preformulation: Active Pharmaceutical Ingredient-Excipient Compatibility Studies

A relevant area of research in the preformulation phase for the development of new dosages is active pharmaceutical ingredient (API)-excipient compatibility. The possibilities of chemical and physical interaction of API and the excipients may affect how efficient and effective it is, while displaying an impact on the nature, stability and availability of API. The most common signs of deterioration of an API are changes in the color, taste, odor, polymorphic form, or crystallization (pharmaceutical incompatibility). These changes arise from chemical reactions with the excipient, leading to degradation of the API. The active components are usually more stable than solid dosage forms, and although testing the compatibility of API-excipients is essential, no protocol has yet been accepted to evaluate their interactions. Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Isothermal Stress Testing-High Performance Liquid Chromatography (IST-HPLC), Hot Stage Microscopy (HSM), Scanning Electron Microscopy (SEM), Solid state Nuclear Magnetic Resonance Spectroscopy (ssNMR) and Power X-ray Diffraction (PXRD) are commonly used as screening techniques for assessing the compatibility of an active pharmaceutical ingredient (API) with some currently employed excipients. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. Once the solid-state reactions of a pharmaceutical system are understood, the necessary steps can be taken to avoid reactivity and improve the stability of drug substances and products. In this chapter, we summarize the techniques to investigate the compatibility between APIs and excipients.

Keywords: Compatibility, Differential scanning calorimetry, Fourier transforminfrared spectroscopy, Isothermal stress testing-high performance liquid chromatography, Solid state nuclear magnetic resonance spectroscopy, Scanning electron microscopy, Power x-ray diffraction.