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

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.

Using Amphiphilic Polymer Micelles as the Templates of Antisolvent Crystallization to Produce Drug Nanocrystals

“…Nanometerization of drug crystals is a robust approach to improve their solubility and bioavailability. , Over the last decade, extensive research has been carried out to prepare nanocrystals of various pharmaceuticals for increased solubility, outstanding reproducibility, and excellent patient compliance . So far, both top–down and bottom–up methods have been utilized to prepare drug nanocrystals. , A top–down approach, which generally includes media grinding and high-pressure homogenization, relies on mechanical forces to reduce large crystalline particles in the millimeter/micron scale to nanoparticles, , whereas a bottom-up approach involves the formation of drug nanocrystals from solutions of ions or molecules through synthesis or self-assembly, including rapid precipitation (reaction or antisolvent crystallization), supercritical fluid crystallization, water (solvent) thermal synthesis, microemulsion, solvent volatilization, etc . Because it is simple and easy to scale up, the traditional top–down method has been commercialized.…”

Machine Learning for the Identification of Hydration Mechanisms of Pharmaceutical-Grade Cellulose Polymers and Their Mixtures with Model Drugs

“…Moreover, it is the only method for the direct study of changes in enthalpy of the examined physical processes. Phase transition analysis in modern drug studies has significantly attracted the attention of many research groups dealing with drug discovery and development [2][3][4][5]. The study of thermodynamic parameters such as melting (T m ), crystallization (T c ), or glass transition temperature (T g ), enthalpy (∆H), and heat capacity (Cp) is a source of valuable information that can be used in the development of new drugs and/or in the improvement of those already used in therapy [6][7][8].…”

“…Sci. 2021, 11, x FOR PEER REVIEW 2 of 15 and development [2][3][4][5]. The study of thermodynamic parameters such as melting (Tm), crystallization (Tc), or glass transition temperature (Tg), enthalpy (ΔH), and heat capacity (Cp) is a source of valuable information that can be used in the development of new drugs and/or in the improvement of those already used in therapy [6][7][8].…”