Advances of Combinative Nanocrystal Preparation Technology for Improving the Insoluble Drug Solubility and Bioavailability

Abstract

The low solubility and bioavailability of aqueous insoluble drugs are critical challenges in the field of pharmaceuticals that need to be overcome. Nanocrystal technology, a novel pharmacological route to address the poor aqueous solubility problem of many poorly soluble drugs, has recently demonstrated great potential for industrial applications and developments. This review focuses on today's preparation technologies, containing top-down, bottom-up, and combinative technology. Among them, the highlighted combinative technology can improve the efficiency of particle size reduction and overcome the shortcomings of a single technology. Then, the characterization methods of nanocrystal production are presented in terms of particle size, morphology, structural state, and surface property. After that, we introduced performance evaluations on the stability, safety, and the in vitro/in vivo dissolution of drug nanocrystals. Finally, the applications and prospects of nanocrystals in drug development are presented. This review may provide some references for the further development and optimization of poorly soluble drug nanocrystals.

Recent developments in the use of nanocrystals to improve bioavailability of APIs

“…HPH breaks down drug particles utilizing high shear powers, drug particle collision powers, turbulent flow and cavitation powers generated in a HPH chamber (Ran et al, 2022). According to different solutions and instruments used, it can be further divided into Microfluidization, IDD-P TM , Dissocubes ® , and Nanopure ® .…”

“…Similarly, Sun et al prepared itraconazole nanosuspension using the HPH method (Sun et al, 2011). The products currently on the market including paliperidone palmitate intramuscular (IM) suspension Invega Sustenna, fenofibrate tablets Triglide ® , and Luteolin nanocrystals (Liu et al, 2021) are prepared by the HPH technique (Ran et al, 2022).…”

“…Depending on the nozzle positions, it can be further developed as the rapid expansion of a supercritical solution into a liquid solvent (RESOLV) method, in which the nozzle is placed in an aqueous solution while the RESS method sets the nozzle in the air. These can lead to fast nucleation and fine particle generation (Padrela et al, 2018; Ran et al, 2022). For RESOLV, in some cases, the organic solvent such as methanol is used.…”

“…The bottom‐up process is mainly based on two basic principles, precipitation and evaporation (Liu et al, 2021; Ran et al, 2022). The nanocrystals are formed in solution through two main steps, that is, nucleation and consequent crystal growth.…”

Development of Telmisartan Nanocrystal-Based Dissolving Microneedle for Brain Targeting via Trigeminal Pathway: A Potentially Promising Treatment for Alzheimer’s with an Improved Pharmacokinetic Profile

“…NC particles were less than 1 μm and were made of 100% drug compounds without polymers, facilitating TMN’s accessibility to the brain and enhancing its therapeutic efficiency . Previous studies had successfully formulated hydrophobic drugs like TMN into NC form, obtaining satisfactory results. , Therefore, TMN would be developed as an NC to improve solubility and maximize its therapeutic effects. However, no direct delivery system approach has been discovered for transporting TMN-NC combinations to the brain, leading to ongoing research and further exploration of this delivery system approach.…”