4.4.1. Fourier Transform Infrared (FTIR) Spectroscopy

FTIR spectroscopy is used for the physical and chemical characterization of powder mixtures in the solid state by evaluating functional groups, identifying bond formation, and comparing bond formation [108,109]. It is a fundamental approach for the study of API-excipient interactions since it permits rapid and simple elucidation of chemical and structural attributes of organic materials as it is sensitive to molecular vibrations that are specific for specific functional groups [108]. Molecular vibrations are categorized based on the energy related to the functional groups within molecules over the 650–4000 cm−<sup>1</sup> wavenumber range [109].

FTIR is mostly used to identify the purity of drug compounds in the crystal, to ascertain the polymorph in the NCM, and some cases are used to determine whether a solvate form of the NCM is present. FTIR can be of specific use in the determination of polymorphic changes during the nanosizing process. For instance, during HPH, piroxicam demonstrated to undergo polymorphic transformation [110]. The piroxicam nanocrystals were stabilized using poloxamer 188. FTIR was used in conjunction with other characterization techniques and confirmed that the crystalline form I of piroxicam made up the majority of the unprocessed piroxicam. A change of colour from white to yellow following HPH indicated a polymorphic conversion from form I to form III and the monohydrate. Confirmation using XRD, FTIR, and DSC confirmed that NC were a mixture of form III and the monohydrate [110].

Lamivudine-zidovudine NCC were synthesized with or without stabilizer [19,111]. The NCC formulation was stabilized with different stabilizers including SDS, TPGS 1000, Tween® 80, and Span® 80. The FTIR spectrum of the NCC was compared to those of the individual drug compounds to verify the absence of chemical interactions. The FTIR spectrum of the NCC revealed the presence of a monohydrate with the presence of a water peak without any peaks corresponding to the API [19,111].

FTIR was used to identify polymorphic changes in wet-milling using an HPH for an experimental anti-cancer compound, SN 30191. The process-induced transformations were studied as a function of time and pressure using infrared spectroscopy, and it was determined that conversion from form II to form I was pressure-dependent [112].
