Excipient-Free Pure Drug Nanoparticles Fabricated by Microfluidic Hydrodynamic Focusing

Abstract

Nanoprecipitation is one of the most versatile methods to produce pure drug nanoparticles (PDNPs) owing to the ability to optimize the properties of the product. Nevertheless, nanoprecipitation may result in broad particle size distribution, low physical stability, and batch-to-batch variability. Microfluidics has emerged as a powerful tool to produce PDNPs in a simple, reproducible, and cost-effective manner with excellent control over the nanoparticle size. In this work, we designed and fabricated T- and Y-shaped Si-made microfluidic devices and used them to produce PDNPs of three kinase inhibitors of different lipophilicity and water-solubility, namely imatinib, dasatinib and tofacitinib, without the use of colloidal stabilizers. PDNPs display hydrodynamic diameter in the 90–350 nm range as measured by dynamic light scattering and a rounded shape as visualized by high-resolution scanning electron microscopy. Powder X-ray diffraction and differential scanning calorimetry confirmed that this method results in highly amorphous nanoparticles. In addition, we show that the flow rate of solvent, the anti-solvent, and the channel geometry of the device play a key role governing the nanoparticle size.

Facile production of quercetin nanoparticles using 3D printed centrifugal flow reactors

“…A second advantage of the RIAC is its ease of manufacture. The fabrication of microfluidic reactors can be relatively complex, costly, and dependent on multiple steps, as shown in the work by Arzi et al 61 RIAC manufacturing instead does not require any post-processing step, as the reactor is ready to use right after 3D printing. This allows for simpler and more cost-effective optimization of the device during development, as well as reproducible and frequent device substitution when required.…”

“…All experiments were conducted at room temperature (∼21 °C), which is consistent with previous studies reporting on microfluidic-based production of drug nanocrystals. 32,61–63…”

“…All experiments were conducted at room temperature ($21 C), which is consistent with previous studies reporting on microuidic-based production of drug nanocrystals. 32,[61][62][63] Characterization of quercetin nanocrystals Dynamic light scattering (DLS) measurements were performed to determine quercetin nanocrystal mean diameter and size dispersity, using the Zetasizer Ultra instrument (Malvern Instrument Ltd, UK). For each measurement, 20 mL of suspension were diluted with 980 mL of deionised (DI) water, which were previously ltered using a 0.20 mm syringe lter.…”

Cannabidiol-Loaded Mixed Polymeric Micelles of Chitosan/Poly(Vinyl Alcohol) and Poly(Methyl Methacrylate) for Trans-Corneal Delivery

“…Samples (5.0-15.0 mg) were sealed in 40 µL Al-crucibles pans (Metter-Toledo, Schwerzenbach, Switzerland) and subjected to different heating-cooling cycles (10 • C/min). For CS-PMMA30, PVA-PMMA16, and the CBD-free and CBD-loaded mixed PMs, the protocol was the following: (i) cooling from 35 CBD-free and CBD-loaded mixed CS-g-PMMA30:PVA-g-PMMA16 (1:1 weight ratio) PMs were prepared by using a microfluidics system designed and fabricated in our laboratory [47]. The microfluidics chip is composed of three layers: the upper and lower layers are glass-made, and the middle layer is made of a 700 µm width p-type silicon wafer (100) upon which the microfluidic channels were embedded.…”

“…PMs can be produced by different methods such as simple dissolution and organic solvent diffusion and evaporation [72]. In this work, mixed CS-PMMA30:PVA-PMMA16 PMs with a 1:1 weight ratio were prepared by a solvent casting method in a microfluidics device [47] and their D h , PDI, Z-potential, and concentration in suspension were measured by DLS and NTA, at 25 and 37 • C. In addition, NTA was used to visualize their Brownian motion in suspension. All the mixed PMs, regardless of crosslinking and CBD loading or not, showed a monomodal size distribution (only one size population could be observed), as exemplified in Figure S5 (see Supplementary Materials) for 0.1% w/v CBD-free crosslinked mixed PMs.…”