*Review* **Application of Fundamental Techniques for Physicochemical Characterizations to Understand Post-Formulation Performance of Pharmaceutical Nanocrystalline Materials**

**Bwalya A. Witika 1,2,\*, Marique Aucamp <sup>3</sup> , Larry L. Mweetwa <sup>2</sup> and Pedzisai A. Makoni 4,\***


**Abstract:** Nanocrystalline materials (NCM, i.e., crystalline nanoparticles) have become an important class of materials with great potential for applications ranging from drug delivery and electronics to optics. Drug nanocrystals (NC) and nano co-crystals (NCC) are examples of NCM with fascinating physicochemical properties and have attracted significant attention in drug delivery. NCM are categorized by advantageous properties, such as high drug-loading efficiency, good long-term physical stability, steady and predictable drug release, and long systemic circulation time. These properties make them excellent formulations for the efficient delivery of a variety of active pharmaceutical ingredients (API). In this review, we summarize the recent advances in drug NCM-based therapy options. Currently, there are three main methods to synthesize drug NCM, including top-down, bottom-up, and combination methods. The fundamental characterization methods of drug NCM are elaborated. Furthermore, the applications of these characterizations and their implications on the post-formulation performance of NCM are introduced.

**Keywords:** nanocrystalline materials; physicochemical characterization; vibrational spectroscopy; X-ray analysis; thermal analysis; critical quality attributes
