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.
Highlights
Nanotechnology has made a significant contribution to overcomepharmaceutical drawbacks of drugs such as poor aqueous solubility, low physicochemical stability in the biological milieu, short half-life and low bioavailability and efficacy [1,2,3,4]
Only one size population was observed for both drugs throughout the whole experiment, which would be in line with the size growth of larger nanoparticles at the expense of smaller ones that underwent gradual dissolution, a phenomenon known as Ostwald ripening [75]
These results could be explained by the lower physical stability of excipient-free pure drug nanoparticles (PDNPs) than surfactant-stabilized ones and indicate that to prevent particle growth over time, products need to undergo drying immediately after production by means of a method that does not require the incorporation of additives and enables redispersion to regenerate particles of the original size, such as spray-drying [90]
Summary
Nanotechnology has made a significant contribution to overcome (bio)pharmaceutical drawbacks of drugs such as poor aqueous solubility, low physicochemical stability in the biological milieu, short half-life and low bioavailability and efficacy [1,2,3,4]. Top-down techniques involve the breakdown of large particles into smaller ones by mechanical forces (e.g., high pressure homogenization, wet ball milling) [19,20], whereas bottom-up techniques (e.g., nanoprecipitation, sono-crystallization, and drying technologies) produce particles through precipitation from a solution at the nanometer scale. The former methods are straightforward and reliable for industrial scale-up.
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