Large-Scale Preparation of Amorphous Cefixime Nanoparticles by Antisolvent Precipitation in a High-Gravity Rotating Packed Bed

Abstract

To enhance the solubility and dissolution rate, and thus potentially improve the oral bioavailability of cefixime (CFX), amorphous CFX nanoparticles were prepared via high-gravity antisolvent precipitation (HGAP) without the aid of any pharmaceutical additives in a rotating packed bed (RPB). The effects of operating variables on particle size and distribution were investigated. Compared to raw CFX, the mean size of prepared nanoparticles decreased greatly from about 2.1 μm to 57 nm, and the saturation solubility increased tremendously from 0.289 to 0.951 mg/mL. CFX nanoparticles showed good stability and were capable of generating a maximum supersaturation level, reaching up to ∼22.8 times of raw CFX's saturation solubility. Further, CFX nanoparticles achieved 100% drug dissolution within 2 min, while the raw drug did not dissolve completely after 45 min, suggesting that the solubility and dissolution properties of CFX nanoparticles were significantly improved. Since the drug recovery ratio achieved 99.9%, and the production capacity of lab-scale RPB with a continuous operation reached 1.8 kg/h, the HGAP method might offer a general and facile platform for mass production of CFX nanoparticles.

Controllable Synthesis of Upconversion Nanophosphors toward Scale‐Up Productions

“…High‐gravity technology, also known as HIGEE technology, is a common method for process intensification within particle synthesis. First reported by Ramshaw (1979), [ 119,120 ] it has been widely used in the synthesis of different nanoparticles, such as drug particles, [ 121 ] nanophosphors, [ 122 ] photocatalysts, [ 123 ] and semiconductor quantum dots. [ 124,125 ] The high‐gravity method normally is fulfilled by a rotating packed bed reactor (RPB) which intensifies the reaction process via generating a high‐gravity environment.…”

Preparation of amorphous drug nanoparticles by high-gravity reactive precipitation technique

“…The experimental setup for HGRP process is schematically displayed in Fig. 1 [33]. The key part of the RPB is a wire-mesh packed rotator, with inner and outer diameters of 35 and 80 mm, respectively.…”

“…Using the identical RPB, amorphous CFX nanoparticles with high solubility and fast dissolution rate could be prepared by HGRP and the previously reported HGAP [33]. The detailed comparison is displayed in Table 1.…”

“…To improve its solubility and dissolution rate, CFX cyclodextrin complexes and solid dispersions have been produced [30][31][32]. Recently, CFX amorphous nanoparticles have be prepared by high-gravity antisolvent precipitation (HGAP) technology with tetrahydrofuran (THF) and isopropyl ether (IPE) as solvent and antisolvent respectively [33]. However, from the aspect of industrial production, the use of organic solvents in HGAP process will need enormous extra cost of apparatus for safety monitoring, environment protection and solvent fractionation.…”

Continuous preparation of nimesulide nanoparticles by liquid antisolvent precipitation using spinning disc reactor

“…Amongst these methods, nanoparticles have shown an intensification in dissolution rate and bioavailability because of their higher surface area per unit volume, as shown by the Noyes–Whitney equation . Although several different methods such as supercritical fluid technique, high‐pressure homogenization, media milling and liquid antisolvent precipitation are available to obtain nanoparticles, liquid antisolvent precipitation has many advantages such as its low cost, easy scaling up and simple processing at ambient temperature and atmospheric pressure. Form an industrial point of view, these promising properties of liquid antisolvent precipitation are very useful for obtaining the active pharmaceutical ingredient's nanoparticles by mixing the drug solution and an antisolvent .…”